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Original Articles
- PSMA expression in hepatic colorectal cancer metastasis
- Eundong Park, Michel Kmeid, Xin Wang, Haiyan Qiu, Clifton G. Fulmer, Marcello P. Toscano, Nusret Bekir Subasi, Maciej Gracz, Hwajeong Lee
- J Pathol Transl Med. 2026;60(1):107-123. Published online January 14, 2026
- DOI: https://doi.org/10.4132/jptm.2025.10.20
- 1,503 View
- 103 Download
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Abstract
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Supplementary Material - Background
Prostate-specific membrane antigen (PSMA) is expressed in the neovasculature of various malignancies, such as colorectal cancer (CRC) and hepatocellular carcinoma (HCC). However, PSMA expression in hepatic CRC metastasis has not been studied in detail. Methods: The PSMA expression in primary CRC and corresponding hepatic metastasis was evaluated by immunohistochemistry in a metastatic CRC cohort (n = 56), which was divided into subgroups according to treatment history and timing of metastasis. Demographic and histological characteristics of primary CRC were collected and their relationships with PSMA expression were examined. Additionally, the PSMA expression in resected HCC (n = 76) was compared with that of hepatic CRC metastasis. Results: In primary CRC, PSMA level showed a positive association with tumor size. Lower PSMA expression in hepatic metastasis was associated with higher primary CRC grade, advanced pTNM stage at the time of CRC resection, presence of tumor deposit, and unresectability of metastatic lesion. PSMA expression in primary CRC correlated with that in hepatic metastasis only in concurrent and untreated metastasis subgroup. PSMA expression in primary CRC and hepatic metastasis, regardless of treatment history and timing of metastasis, was not significantly different from that of HCC. Conclusions: Several adverse pathological features of primary CRC were associated with a lower PSMA expression in hepatic metastasis. PSMA expression in hepatic metastasis correlated with that of primary CRC only in concurrent and untreated subgroup. Primary HCC and hepatic CRC metastasis show comparable levels of PSMA expression.
- Paricalcitol prevents MAPK pathway activation and inflammation in adriamycin-induced kidney injury in rats
- Amanda Lima Deluque, Lucas Ferreira de Almeida, Beatriz Magalhães Oliveira, Cláudia Silva Souza, Ana Lívia Dias Maciel, Heloísa Della Coletta Francescato, Cleonice Giovanini, Roberto Silva Costa, Terezila Machado Coimbra
- J Pathol Transl Med. 2024;58(5):219-228. Published online August 27, 2024
- DOI: https://doi.org/10.4132/jptm.2024.07.12
- 4,043 View
- 222 Download
- 2 Web of Science
- 2 Crossref
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Abstract
PDF
- Background
Activation of the mitogen-activated protein kinase (MAPK) pathway induces uncontrolled cell proliferation in response to inflammatory stimuli. Adriamycin (ADR)-induced nephropathy (ADRN) in rats triggers MAPK activation and pro-inflammatory mechanisms by increasing cytokine secretion, similar to chronic kidney disease (CKD). Activation of the vitamin D receptor (VDR) plays a crucial role in suppressing the expression of inflammatory markers in the kidney and may contribute to reducing cellular proliferation. This study evaluated the effect of pre-treatment with paricalcitol on ADRN in renal inflammation mechanisms.
Methods
Male Sprague-Dawley rats were implanted with an osmotic minipump containing activated vitamin D (paricalcitol, Zemplar, 6 ng/day) or vehicle (NaCl 0.9%). Two days after implantation, ADR (Fauldoxo, 3.5 mg/kg) or vehicle (NaCl 0.9%) was injected. The rats were divided into four experimental groups: control, n = 6; paricalcitol, n = 6; ADR, n = 7 and, ADR + paricalcitol, n = 7.
Results
VDR activation was demonstrated by increased CYP24A1 in renal tissue. Paricalcitol prevented macrophage infiltration in the glomeruli, cortex, and outer medulla, prevented secretion of tumor necrosis factor-α, and interleukin-1β, increased arginase I and decreased arginase II tissue expressions, effects associated with attenuation of MAPK pathways, increased zonula occludens-1, and reduced cell proliferation associated with proliferating cell nuclear antigen expression. Paricalcitol treatment decreased the stromal cell-derived factor 1α/chemokine C-X-C receptor type 4/β-catenin pathway.
Conclusions
Paricalcitol plays a renoprotective role by modulating renal inflammation and cell proliferation. These results highlight potential targets for treating CKD. -
Citations
Citations to this article as recorded by
- Perirenal fat differs in patients with chronic kidney disease receiving different vitamin D-based treatments: a preliminary study
Ana Checa-Ros, Antonella Locascio, Owahabanun-Joshua Okojie, Pablo Abellán-Galiana, Luis D’Marco
BMC Nephrology.2025;[Epub] CrossRef - Attenuating amiodarone-induced lung toxicity by the vitamin D receptor activator paricalcitol in rats: targeting TLR4/NF-κB/HIF-1α and TGF-β/Smad signaling pathways
Aamal G. El-Waseif, Mahmoud Elshal, Dalia H. El-Kashef, Nashwa M. Abu-Elsaad
Naunyn-Schmiedeberg's Archives of Pharmacology.2025;[Epub] CrossRef
- Perirenal fat differs in patients with chronic kidney disease receiving different vitamin D-based treatments: a preliminary study
- Senescent tumor cells in colorectal cancer are characterized by elevated enzymatic activity of complexes 1 and 2 in oxidative phosphorylation
- Jun Sang Shin, Tae-Gyu Kim, Young Hwa Kim, So Yeong Eom, So Hyun Park, Dong Hyun Lee, Tae Jun Park, Soon Sang Park, Jang-Hee Kim
- J Pathol Transl Med. 2023;57(6):305-314. Published online November 7, 2023
- DOI: https://doi.org/10.4132/jptm.2023.10.09
- 7,383 View
- 317 Download
- 3 Web of Science
- 3 Crossref
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Abstract
PDFSupplementary Material
- Background
Cellular senescence is defined as an irreversible cell cycle arrest caused by various internal and external insults. While the metabolic dysfunction of senescent cells in normal tissue is relatively well-established, there is a lack of information regarding the metabolic features of senescent tumor cells.
Methods
Publicly available single-cell RNA-sequencing data from the GSE166555 and GSE178341 datasets were utilized to investigate the metabolic features of senescent tumor cells. To validate the single-cell RNA-sequencing data, we performed senescence-associated β-galactosidase (SA-β-Gal) staining to identify senescent tumor cells in fresh frozen colorectal cancer tissue. We also evaluated nicotinamide adenine dinucleotide dehydrogenase–tetrazolium reductase (NADH-TR) and succinate dehydrogenase (SDH) activity using enzyme histochemical methods and compared the staining with SA-β-Gal staining. MTT assay was performed to reveal the complex 1 activity of the respiratory chain in in-vitro senescence model.
Results
Single-cell RNA-sequencing data revealed an upregulation in the activity of complexes 1 and 2 in oxidative phosphorylation, despite overall mitochondrial dysfunction in senescent tumor cells. Both SA-β-Gal and enzyme histochemical staining using fresh frozen colorectal cancer tissues indicated a high correlation between SA-β-Gal positivity and NADH-TR/SDH staining positivity. MTT assay showed that senescent colorectal cancer cells exhibit higher absorbance in 600 nm wavelength.
Conclusions
Senescent tumor cells exhibit distinct metabolic features, characterized by upregulation of complexes 1 and 2 in the oxidative phosphorylation pathway. NADH-TR and SDH staining represent efficient methods for detecting senescent tumor cells in colorectal cancer. -
Citations
Citations to this article as recorded by- Senescence, Aging and Disease Throughout the Gastrointestinal System
Sofia Ferreira-Gonzalez, Tomonori Matsumoto, Eiji Hara, Stuart J. Forbes
Gastroenterology.2025; 169(7): 1357. CrossRef - Cellular Aging and Senescence in Cancer: A Holistic Review of Cellular Fate Determinants
Muhammad Tufail, Yu-Qi Huang, Jia-Ju Hu, Jie Liang, Cai-Yun He, Wen-Dong Wan, Can-Hua Jiang, Hong Wu, Ning Li
Aging and disease.2024;[Epub] CrossRef - Real-time assessment of relative mitochondrial ATP synthesis response against inhibiting and stimulating substrates (MitoRAISE)
Eun Sol Chang, Kyoung Song, Ji-Young Song, Minjung Sung, Mi-Sook Lee, Jung Han Oh, Ji-Yeon Kim, Yeon Hee Park, Kyungsoo Jung, Yoon-La Choi
Cancer & Metabolism.2024;[Epub] CrossRef
- Senescence, Aging and Disease Throughout the Gastrointestinal System
- Prognostic significance of viable tumor size measurement in hepatocellular carcinomas after preoperative locoregional treatment
- Yoon Jung Hwang, Youngeun Lee, Hyunjin Park, Yangkyu Lee, Kyoungbun Lee, Haeryoung Kim
- J Pathol Transl Med. 2021;55(5):338-348. Published online September 2, 2021
- DOI: https://doi.org/10.4132/jptm.2021.07.26
- 6,698 View
- 122 Download
- 5 Web of Science
- 5 Crossref
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Abstract
PDFSupplementary Material
- Background
Preoperative locoregional treatment (LRT) for hepatocellular carcinoma (HCC) often induces intratumoral necrosis without affecting the overall tumor size, and residual viable tumor size (VTS) on imaging is an important clinical parameter for assessing post-treatment response. However, for surgical specimens, it is unclear whether the VTS would be more relevant to prognosis compared to total tumor size (TTS).
Methods
A total of 142 surgically resected solitary HCC cases were retrospectively reviewed. The TTS and VTS were assessed by applying the modified Response Evaluation Criteria in Solid Tumors method to the resected specimens, and correlated with the clinicopathological features and survival.
Results
As applying VTS, 13/142 cases (9.2%) were down-staged to ypT1a. Although the survival analysis results for overall survival according to TTS or VTS were similar, VTS was superior to predict disease-free survival (DFS; p = .023) compared to TTS (p = .08). In addition, multivariate analysis demonstrated VTS > 2 cm to be an independent predictive factor for decreased DFS (p = .001). In the subpopulation of patients with LRT (n = 54), DFS in HCCs with TTS or VTS > 2 cm were significantly shorter than those with TTS or VTS ≤ 2 cm (p = .047 and p = .001, respectively). Interestingly, HCCs with TTS > 2 cm but down-staged to VTS ≤ 2 cm after preoperative LRT had similar survival to those with TTS ≤ 2 cm.
Conclusions
Although the prognostic impact of tumor size was similar regardless of whether TTS or VTS was applied, reporting VTS may help to increase the number of candidates for surgery in HCC patients with preoperative LRT. -
Citations
Citations to this article as recorded by- PET-Assessed Metabolic Tumor Volume Across the Spectrum of Solid-Organ Malignancies: A Review of the Literature
Anusha Agarwal, Chase J. Wehrle, Sangeeta Satish, Paresh Mahajan, Suneel Kamath, Shlomo Koyfman, Wen Wee Ma, Maureen Linganna, Jamak Modaresi Esfeh, Charles Miller, David C. H. Kwon, Andrea Schlegel, Federico Aucejo
Biomedicines.2025; 13(1): 123. CrossRef - Measures for response assessment in HCC treatment
Fereshteh Yazdanpanah, Omar Al-Daoud, Moein Moradpour, Stephen Hunt
Hepatoma Research.2024;[Epub] CrossRef - Machine Learning for Dynamic Prognostication of Patients With Hepatocellular Carcinoma Using Time-Series Data: Survival Path Versus Dynamic-DeepHit HCC Model
Lujun Shen, Yiquan Jiang, Tao Zhang, Fei Cao, Liangru Ke, Chen Li, Gulijiayina Nuerhashi, Wang Li, Peihong Wu, Chaofeng Li, Qi Zeng, Weijun Fan
Cancer Informatics.2024;[Epub] CrossRef - Construction and validation of a novel signature based on epithelial-mesenchymal transition–related genes to predict prognosis and immunotherapy response in hepatocellular carcinoma by comprehensive analysis of the tumor microenvironment
Biao Gao, Yafei Wang, Shichun Lu
Functional & Integrative Genomics.2023;[Epub] CrossRef - Cellular senescence affects energy metabolism, immune infiltration and immunotherapeutic response in hepatocellular carcinoma
Biao Gao, Yafei Wang, Shichun Lu
Scientific Reports.2023;[Epub] CrossRef
- PET-Assessed Metabolic Tumor Volume Across the Spectrum of Solid-Organ Malignancies: A Review of the Literature
Reviews
- Hepatocellular adenomas: recent updates
- Haeryoung Kim, Young Nyun Park
- J Pathol Transl Med. 2021;55(3):171-180. Published online April 7, 2021
- DOI: https://doi.org/10.4132/jptm.2021.02.27
- 12,063 View
- 552 Download
- 8 Web of Science
- 10 Crossref
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Abstract
PDF
- Hepatocellular adenoma (HCA) is a heterogeneous entity, from both the histomorphological and molecular aspects, and the resultant subclassification has brought a strong translational impact for both pathologists and clinicians. In this review, we provide an overview of the recent updates on HCA from the pathologists’ perspective and discuss several practical issues and pitfalls that may be useful for diagnostic practice.
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Citations
Citations to this article as recorded by- Preventing false positive imaging diagnosis of HCC: differentiating HCC from mimickers and practical strategies
Ijin Joo
Journal of Liver Cancer.2025; 25(2): 217. CrossRef - Prognostic role of selection criteria for liver transplantation in patients with hepatocellular carcinoma: Review and bibliometric
Pamela Scarlett Espinoza Loyola, Diana Laura Muratalla Bautista, Karen Adela Hernández Bautista, Elizabeth Gil White, José Antonio González Moreno, Daniel Angel Torres del Real, Víctor Manuel Páez Zayas, Carla Escorza-Molina, Fernando Mondragón Rodríguez,
iLIVER.2024; 3(1): 100077. CrossRef - ACG Clinical Guideline: Focal Liver Lesions
Catherine Frenette, Mishal Mendiratta-Lala, Reena Salgia, Robert J. Wong, Bryan G. Sauer, Anjana Pillai
American Journal of Gastroenterology.2024; 119(7): 1235. CrossRef - Hepatocellular adenoma update: diagnosis, molecular classification, and clinical course
Sarah Poetter-Lang, Ahmed Ba-Ssalamah, Nina Bastati, Sami A Ba-Ssalamah, Jacqueline C Hodge, Giuseppe Brancatelli, Valérie Paradis, Valérie Vilgrain
British Journal of Radiology.2024; 97(1163): 1740. CrossRef - Fatal rupture of hepatic adenomatosis: Autopsy case and review of the literature
Sarra Ben Abderrahim, Khouloud Chérif, Zeineb Nfikha, Sarra Gharsallaoui, Imen El Aini, Maher Jedidi, Moncef Mokni, Mohamed Ben Dhiab
Journal of Forensic Sciences.2023; 68(4): 1393. CrossRef - Large Hepatocellular Adenoma Presenting with Iron Deficiency Anemia: A Case Report
Young Kwon Koh, Su Hyun Yoon, Sung Han Kang, Hyery Kim, Ho Joon Im, Suhyeon Ha, Jung-Man Namgoong, Kyung-Nam Koh
Clinical Pediatric Hematology-Oncology.2023; 30(1): 25. CrossRef - A Case Report on a Giant Hepatic Inflammatory Adenoma in a Young Female That Presented as Spontaneous Intrahepatic Hematoma
Andreas Kyvetos, Panagiota Voukelatou, Ioannis Vrettos, Spyridon Pantzios , Ioannis Elefsiniotis
Cureus.2023;[Epub] CrossRef - Advances in Histological and Molecular Classification of Hepatocellular Carcinoma
Joon Hyuk Choi, Swan N. Thung
Biomedicines.2023; 11(9): 2582. CrossRef - Estrobolome and Hepatocellular Adenomas—Connecting the Dots of the Gut Microbial β-Glucuronidase Pathway as a Metabolic Link
Sandica Bucurica, Mihaela Lupanciuc, Florentina Ionita-Radu, Ion Stefan, Alice Elena Munteanu, Daniela Anghel, Mariana Jinga, Elena Laura Gaman
International Journal of Molecular Sciences.2023; 24(22): 16034. CrossRef - Hepatocellular adenoma: what we know, what we do not know, and why it matters
Paulette Bioulac‐Sage, Annette S H Gouw, Charles Balabaud, Christine Sempoux
Histopathology.2022; 80(6): 878. CrossRef
- Preventing false positive imaging diagnosis of HCC: differentiating HCC from mimickers and practical strategies
- Liquid biopsy using extracellular vesicle–derived DNA in lung adenocarcinoma
- In Ae Kim, Jae Young Hur, Hee Joung Kim, Seung Eun Lee, Wan Seop Kim, Kye Young Lee
- J Pathol Transl Med. 2020;54(6):453-461. Published online October 8, 2020
- DOI: https://doi.org/10.4132/jptm.2020.08.13
- 9,432 View
- 176 Download
- 21 Web of Science
- 20 Crossref
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Abstract
PDF
- Blood liquid biopsy has emerged as a way of overcoming the clinical limitations of repeat biopsy by testing for the presence of acquired resistance mutations to therapeutic agents. Despite its merits of repeatability and non-invasiveness, this method is currently only used as a supplemental test due to a relatively low sensitivity rate of 50%–60%, and cannot replace tissue biopsy. The circulating tumor DNAs used in blood liquid biopsies are passive products of fragmented DNA with a short half-life released following tumor cell death; the low sensitivity seen with liquid blood biopsy results from this instability, which makes increasing the sensitivity of this test fundamentally difficult. Extracellular vesicles (EVs) are ideal carriers of cancer biomarkers, as cancer cells secret an abundance of EVs, and the contents of tumor cell-originated EVs reflect the molecular and genetic composition of parental cells. In addition, EV-derived DNAs (EV DNAs) consist of large-sized genomic DNAs and tumor-specific oncogenic mutant DNAs. For these reasons, liquid biopsy using EV DNA has the potential to overcome issues arising from tissue shortages associated with small biopsies, which are often seen in lung cancer patients, and the biopsy product can be used in other diagnostic methods, such as epidermal growth factor receptor (EGFR) mutation testing and next-generation sequencing (NGS). A higher sensitivity can be achieved when EV DNAs obtained from bronchoalveolar lavage fluid (BALF) are used rather than those from blood. BALF, when obtained close to the tumor site, is a promising liquid biopsy tool, as it enables the gathering of both cellular and non-cellular fractions of the tumor microenvironment, and provides increased diagnostic sensitivity when compared to blood.
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Citations
Citations to this article as recorded by- Application of extracellular vesicles in tumor liquid biopsy
Shuai Li, Yating Liu, Dayong Yang
Chinese Science Bulletin.2026; 71(2): 421. CrossRef - Liquid biopsy biomarkers for accurate detection of malignant pulmonary nodules: a meta-analytic approach
Alberto Caballero-Vazquez, Marta Garcia-Cerezo, Laura R. Fernandez-Castro, Concepcion Morales-Garcia, Antonio Jesus Lainez Ramos-Bossini, Fabian Vergara-Rubio, Francisco Gabriel Ortega-Sanchez, Jose Manuel Sanchez-Maldonado
Discover Oncology.2026;[Epub] CrossRef - Meta‐Analysis of Non‐Blood Liquid Biopsy Specimens: Diagnostic Performance in Cancer Detection
Kartavya Kumar Verma
Diagnostic Cytopathology.2026; 54(3): 235. CrossRef - Circulating Extracellular Vesicles as Promising Biomarkers for Precession Diagnostics: A Perspective on Lung Cancer
Sunil Vasu, Vinith Johnson, Archana M, K. Anki Reddy, Uday Kumar Sukumar
ACS Biomaterials Science & Engineering.2025; 11(1): 95. CrossRef - Diagnostic performance of metagenomic next-generation sequencing among hematological malignancy patients with bloodstream infections after antimicrobial therapy
Yueyi Xu, Miaoxin Peng, Tong Zhou, Yonggong Yang, Peipei Xu, Ting Xie, Xuefang Cao, Bing Chen, Jian Ouyang
Journal of Infection.2025; 90(2): 106395. CrossRef - Unraveling extracellular vesicle DNA: Biogenesis, functions, and clinical implications
Mehraneh Nouri, Fateme Nasiri, Samaneh Sharif, Mohammad Reza Abbaszadegan
Pathology - Research and Practice.2025; 269: 155937. CrossRef - Nanobiotechnology: A smart platform of the future transform liquid biopsy era
Srijan Goswami, Palas Samanta, Manab Deb Adhikari
The Journal of Liquid Biopsy.2024; 3: 100137. CrossRef - Mesenchymal stem/stromal cells: dedicator to maintain tumor homeostasis
Juncun Yao, Li Sun, Feng Gao, Wei Zhu
Human Cell.2024;[Epub] CrossRef - Extracellular Vesicle-DNA: The Next Liquid Biopsy Biomarker for Early Cancer Diagnosis?
Irène Tatischeff
Cancers.2023; 15(5): 1456. CrossRef - Isolation of extracellular vesicles from human plasma samples: The importance of controls
Migmar Tsamchoe, Stephanie Petrillo, Anthoula Lazaris, Peter Metrakos
Biotechnology Journal.2023;[Epub] CrossRef - The role of extracellular vesicles in non-small-cell lung cancer, the unknowns, and how new approach methodologies can support new knowledge generation in the field
Sive Mullen, Dania Movia
European Journal of Pharmaceutical Sciences.2023; 188: 106516. CrossRef - Silicon microfabrication technologies for biology integrated advance devices and interfaces
Vuslat B. Juska, Graeme Maxwell, Pedro Estrela, Martyn E. Pemble, Alan O'Riordan
Biosensors and Bioelectronics.2023; 237: 115503. CrossRef - Bronchoalveolar Lavage as Potential Diagnostic Specimens to Genetic Testing in Advanced Nonsmall Cell Lung Cancer
Xuwen Lin, Yazhou Cai, Chenyu Zong, Binbin Chen, Di Shao, Hao Cui, Zheng Li, Ping Xu
Technology in Cancer Research & Treatment.2023;[Epub] CrossRef - In-Cell Labeling Coupled to Direct Analysis of Extracellular Vesicles in the Conditioned Medium to Study Extracellular Vesicles Secretion with Minimum Sample Processing and Particle Loss
Anissa Viveiros, Vaibhavi Kadam, John Monyror, Luis Carlos Morales, Desmond Pink, Aja M. Rieger, Simonetta Sipione, Elena Posse de Chaves
Cells.2022; 11(3): 351. CrossRef - Recent advances in liquid biopsy in cancers: Diagnosis, disease state and treatment response monitoring
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Clinical and Translational Discovery.2022;[Epub] CrossRef - Cell-Secreted Vesicles: Novel Opportunities in Cancer Diagnosis, Monitoring and Treatment
Cristina Catoni, Veronica Di Paolo, Elisabetta Rossi, Luigi Quintieri, Rita Zamarchi
Diagnostics.2021; 11(6): 1118. CrossRef - DNA-Loaded Extracellular Vesicles in Liquid Biopsy: Tiny Players With Big Potential?
Susana García-Silva, Miguel Gallardo, Héctor Peinado
Frontiers in Cell and Developmental Biology.2021;[Epub] CrossRef - Characteristics and Clinical Application of Extracellular Vesicle-Derived DNA
Jae Young Hur, Kye Young Lee
Cancers.2021; 13(15): 3827. CrossRef - Bronchoalveolar Lavage as a Potential Diagnostic Specimens to Genetic Testing in Advanced Lung Cancer
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SSRN Electronic Journal .2021;[Epub] CrossRef - Multi-Omics Data Integration in Extracellular Vesicle Biology—Utopia or Future Reality?
Leona Chitoiu, Alexandra Dobranici, Mihaela Gherghiceanu, Sorina Dinescu, Marieta Costache
International Journal of Molecular Sciences.2020; 21(22): 8550. CrossRef
- Application of extracellular vesicles in tumor liquid biopsy
Original Articles
- Guanabenz Acetate Induces Endoplasmic Reticulum Stress–Related Cell Death in Hepatocellular Carcinoma Cells
- Hyo Jeong Kang, Hyang Sook Seol, Sang Eun Lee, Young-Ah Suh, Jihun Kim, Se Jin Jang, Eunsil Yu
- J Pathol Transl Med. 2019;53(2):94-103. Published online January 16, 2019
- DOI: https://doi.org/10.4132/jptm.2019.01.14
- 9,672 View
- 199 Download
- 13 Web of Science
- 13 Crossref
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Abstract
PDFSupplementary Material
- Background
Development of chemotherapeutics for the treatment of advanced hepatocellular carcinoma (HCC) has been lagging. Screening of candidate therapeutic agents by using patient-derived preclinical models may facilitate drug discovery for HCC patients.
Methods
Four primary cultured HCC cells from surgically resected tumor tissues and six HCC cell lines were used for high-throughput screening of 252 drugs from the Prestwick Chemical Library. The efficacy and mechanisms of action of the candidate anti-cancer drug were analyzed via cell viability, cell cycle assays, and western blotting.
Results
Guanabenz acetate, which has been used as an antihypertensive drug, was screened as a candidate anti-cancer agent for HCC through a drug sensitivity assay by using the primary cultured HCC cells and HCC cell lines. Guanabenz acetate reduced HCC cell viability through apoptosis and autophagy. This occurred via inhibition of growth arrest and DNA damage-inducible protein 34, increased phosphorylation of eukaryotic initiation factor 2α, increased activating transcription factor 4, and cell cycle arrest.
Conclusions
Guanabenz acetate induces endoplasmic reticulum stress–related cell death in HCC and may be repositioned as an anti-cancer therapeutic agent for HCC patients. -
Citations
Citations to this article as recorded by- ER stress signaling at the interphase between MASH and HCC
Younis Hazari, Eric Chevet, Béatrice Bailly-Maitre, Claudio Hetz
Hepatology.2026; 83(2): 387. CrossRef - The Integrated Stress Response in Cancer: Paradox and Therapeutic Promise
Chenliang Zhang, Ting Zhang, Qiulin Tang, Yu Zeng, Dan Cao
Comprehensive Physiology.2026;[Epub] CrossRef - The Construction of ceRNA Regulatory Network Unraveled Prognostic Biomarkers and Repositioned Drug Candidates for the Management of Pancreatic Ductal Adenocarcinoma
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Guanabenz acetate, an antihypertensive drug repurposed as an inhibitor of
Escherichia coli
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- ER stress signaling at the interphase between MASH and HCC
- Quilty Lesions in the Endomyocardial Biopsies after Heart Transplantation
- Haeyon Cho, Jin-Oh Choi, Eun-Seok Jeon, Jung-Sun Kim
- J Pathol Transl Med. 2019;53(1):50-56. Published online December 26, 2018
- DOI: https://doi.org/10.4132/jptm.2018.11.30
- 8,549 View
- 132 Download
- 6 Web of Science
- 7 Crossref
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Abstract
PDFSupplementary Material
- Background
The aim of this study was to investigate the clinical significance of Quilty lesions in endomyocardial biopsies (EMBs) of cardiac transplantation patients.
Methods
A total of 1190EMBs from 117 cardiac transplantation patients were evaluated histologically for Quilty lesions,acute cellular rejection, and antibody-mediated rejection. Cardiac allograft vasculopathy wasdiagnosed by computed tomography coronary angiography. Clinical information, including thepatients’ survival was retrieved by a review of medical records.
Results
Eighty-eight patients(75.2%) were diagnosed with Quilty lesions, which were significantly associated with acute cellularrejection, but not with acute cellular rejection ≥ 2R or antibody-mediated rejection. In patientsdiagnosed with both Quilty lesions and acute cellular rejection, the time-to-onset of Quilty lesionsfrom transplantation was longer than that of acute cellular rejections. We found a significant associationbetween Quilty lesions and cardiac allograft vasculopathy. No significant relationship wasfound between Quilty lesions and the patients’ survival.
Conclusions
Quilty lesion may be an indicator of previous acute cellular rejection rather than a predictor for future acute cellular rejection. -
Citations
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- C-reactive Protein Overexpression in the Background Liver of Hepatitis B Virus–Associated Hepatocellular Carcinoma Is a Prognostic Biomarker
- Jin Ho Shin, Eunsil Yu, Eun Na Kim, Chong Jai Kim
- J Pathol Transl Med. 2018;52(5):267-274. Published online July 27, 2018
- DOI: https://doi.org/10.4132/jptm.2018.07.14
- 9,142 View
- 179 Download
- 8 Web of Science
- 8 Crossref
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Abstract
PDF
- Background
Chronic hepatitis B virus (HBV) infection is a leading cause of hepatocellular carcinoma (HCC). Peripheral blood C-reactive protein (CRP) concentration and CRP overexpression in HCC cells are proven to be prognostic markers for HCC, but the significance of CRP expression in non-neoplastic hepatocytes, which are the primary origin of CRP, has not been studied. This study was conducted to determine the clinicopathologic significance of CRP immunoreactivity in the background liver of HBV-associated HCC.
Methods
CRP immunostaining was done on tissue microarrays of non-neoplastic liver tissues obtained from surgically resected, treatment-naïve HBV-associated HCCs (n = 156). The relationship between CRP immunoreactivity and other clinicopathologic parameters including cancer-specific survival was analyzed. CRP immunoreactivity was determined using a 4-tier grading system: grades 0, 1, 2, and 3.
Results
CRP was positive in 139 of 156 cases (89.1%) of non-neoplastic liver in patients with HCCs: grade 1 in 83 cases (53.2%); grade 2 in 50 cases (32.1%); and grade 3 in six cases (3.8%). The patients with diffuse CRP immunoreactivity (grade 3) had decreased cancer-specific survival (p = .031) and a tendency for shorter interval before early recurrence (p = .050). The degree of CRP immunoreactivity correlated with serum CRP concentration (p < .001).
Conclusions
CRP immunoreactivity in non-neoplastic liver is a novel biomarker for poor cancer-specific survival of HBV-associated HCC and correlates with serum CRP concentration. -
Citations
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Case Study
- Combined Hepatocellular Carcinoma and Neuroendocrine Carcinoma with Ectopic Secretion of Parathyroid Hormone: A Case Report and Review of the Literature
- Hyun Jung Kwon, Ji-Won Kim, Haeryoung Kim, YoungRok Choi, Soomin Ahn
- J Pathol Transl Med. 2018;52(4):232-237. Published online May 25, 2018
- DOI: https://doi.org/10.4132/jptm.2018.05.17
- 8,964 View
- 159 Download
- 17 Web of Science
- 17 Crossref
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Abstract
PDF
- Primary combined hepatocellular carcinoma (HCC) and neuroendocrine carcinoma is a rare entity, and so is hypercalcemia due to ectopic parathyroid hormone (PTH) secretion by tumor. A 44-year old man with hepatitis B virus associated chronic liver disease presented with a hepatic mass. Hemihepatectomy discovered the mass as combined HCC and poorly differentiated cholangiocarcinoma. During adjuvant chemoradiation therapy, he presented with nausea, and multiple systemic metastases were found. Laboratory tests revealed hypercalcemia with markedly elevated PTH and neuron specific enolase. Parathyroid scan showed normal uptake in parathyroid glands, suggestive of ectopic PTH secretion. Subsequently, immunohistochemistry of neuroendocrine marker was performed on the primary lesion, and confirmed the neuroendocrine differentiation in non-HCC component. The patient died 71 days after surgery. This report may suggest the possibility of ectopic PTH secretion by neuroendocrine carcinoma of hepatic origin causing hypercalcemia. Caution for neuroendocrine differentiation should be exercised when diagnosing poorly differentiated HCC.
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Citations
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Review
- Extracellular Vesicles and the Promise of Continuous Liquid Biopsies
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- J Pathol Transl Med. 2018;52(1):1-8. Published online January 15, 2018
- DOI: https://doi.org/10.4132/jptm.2017.05.21
- 19,223 View
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Abstract
PDF
- The rapid and accurate diagnosis of patients with minimally invasive procedures was once only found in science fiction. However, the discovery of extracellular vesicles (EVs) and their near ubiquity in body fluids, coupled with the advent of inexpensive next generation sequencing techniques and EV purification protocols, promises to make science fiction a reality. Purifying and sequencing the RNA content of EV from routine blood draws and urine samples are likely to enable pathologists and physicians to diagnose and track the progress of diseases in many inaccessible tissues in the near future. Here we present the evolutionary background of EV, summarize the biology of EV formation and cargo selection, and discuss the current barriers to making continuous liquid biopsies through the use of EV a science reality.
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Blood-derived APLP1
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extracellular vesicles are potential biomarkers for the early diagnosis of brain diseases
Case Study
- Hepatocellular Carcinoma Arising in a Huge Hepatocellular Adenoma with Bone Marrow Metaplasia
- Hyo Jeong Kang, Hui Jeong Jeong, So-Woon Kim, Eunsil Yu, Young-Joo Lee, So Yeon Kim, Jihun Kim
- J Pathol Transl Med. 2018;52(4):226-231. Published online December 27, 2017
- DOI: https://doi.org/10.4132/jptm.2017.11.12
- 8,985 View
- 152 Download
- 5 Web of Science
- 6 Crossref
-
Abstract
PDF
- Hepatocellular adenoma (HCA) is the most common type of benign liver tumor, and its major complication is malignant transformation to hepatocellular carcinoma (HCC). Here, we report a case of HCC arising in HCA with bone marrow metaplasia in a 24-year-old Korean woman who presented with abdominal discomfort. A huge liver mass was found on abdominal ultrasonography. She underwent surgical hepatic resection, and the resected specimen was entirely involved by a 20-cm-sized tumor. Histological review revealed a well differentiated HCC arising from inflammatory HCA with β-catenin nuclear positivity and bone marrow metaplasia that contained hematopoietic cells. This case was unique because malignant transformation, inflammatory type HCA, β-catenin nuclear staining, and bone marrow metaplasia were simultaneously observed. Additionally, it should be noted that a large HCA with β-catenin activation can undergo malignant transformation and should be surgically resected in a timely manner.
-
Citations
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Original Articles
- The Clinicopathological and Prognostic Significance of the Gross Classification of Hepatocellular Carcinoma
- Yangkyu Lee, Hyunjin Park, Hyejung Lee, Jai Young Cho, Yoo-Seok Yoon, Young-Rok Choi, Ho-Seong Han, Eun Sun Jang, Jin-Wook Kim, Sook-Hyang Jeong, Soomin Ahn, Haeryoung Kim
- J Pathol Transl Med. 2018;52(2):85-92. Published online November 24, 2017
- DOI: https://doi.org/10.4132/jptm.2017.11.13
- 15,014 View
- 390 Download
- 27 Web of Science
- 24 Crossref
-
Abstract
PDF
- Background
We aimed to determine the clinicopathological significance of the gross classification of hepatocellular carcinoma (HCC) according to the Korean Liver Cancer Association (KLCA) guidelines.
Methods
A retrospective analysis was performed on 242 cases of consecutively resected solitary primary HCC between 2003 and 2012 at Seoul National University Bundang Hospital. The gross classification (vaguely nodular [VN], expanding nodular [EN], multinodular confluent [MC], nodular with perinodular extension [NP], and infiltrative [INF]) was reviewed for all cases, and were correlated with various clinicopathological features and the expression status of “stemness”-related (cytokeratin 19 [CK19], epithelial cell adhesion molecule [EpCAM]), and epithelial-mesenchymal transition (EMT)–related (urokinase plasminogen activator receptor [uPAR] and Ezrin) markers.
Results
Significant differences were seen in overall survival (p=.015) and disease-free survival (p = .034) according to the gross classification; INF type showed the worst prognosis while VN and EN types were more favorable. When the gross types were simplified into two groups, type 2 HCCs (MC/NP/INF) were more frequently larger and poorly differentiated, and showed more frequent microvascular and portal venous invasion, intratumoral fibrous stroma and higher pT stages compared to type 1 HCCs (EN/VN) (p<.05, all). CK19, EpCAM, uPAR, and ezrin expression was more frequently seen in type 2 HCCs (p<.05, all). Gross classification was an independent predictor of both overall and disease-free survival by multivariate analysis (overall survival: p=.030; hazard ratio, 4.118; 95% confidence interval, 1.142 to 14.844; disease-free survival: p=.016; hazard ratio, 1.617; 95% confidence interval, 1.092 to 2.394).
Conclusions
The gross classification of HCC had significant prognostic value and type 2 HCCs were associated with clinicopathological features of aggressive behavior, increased expression of “stemness”- and EMT-related markers, and decreased survival. -
Citations
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Ying-Wen Hou, Tian-Qi Zhang, Li-Di Ma, Yi-Quan Jiang, Xue Han, Tian Di, Lu Tang, Rong-Ping Guo, Min-Shan Chen, Jin-Xin Zhang, Zhi-Mei Huang, Jin-Hua Huang
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- Long-Term Outcomes of Transarterial Chemoembolization plus Ablation versus Surgical Resection in Patients with Large BCLC Stage A/B HCC
- Prognosis of Hepatocellular Carcinoma after Liver Transplantation: Comparative Analysis with Partial Hepatectomy
- Kyuho Lee, Kyoung-Bun Lee, Nam-Joon Yi, Kyung-Suk Suh, Ja-June Jang
- J Pathol Transl Med. 2017;51(1):79-86. Published online December 25, 2016
- DOI: https://doi.org/10.4132/jptm.2016.10.13
- 9,505 View
- 150 Download
- 6 Web of Science
- 5 Crossref
-
Abstract
PDF
- Background
Liver transplantation (LT) is the treatment of choice for hepatocellular carcinoma (HCC). The aim of this study was to investigate the recurrence rate of HCC after LT and prognostic factors for recurrence by comparing LT with non-transplanted resection. Methods: The participants were 338 patients who underwent LT between 1996 and 2012 at Seoul National University Hospital (LT group) and 520 HCC patients who underwent partial hepatectomy between 1995 and 2006 (control group, non-LT group). Results: In the LT group, 68 of 338 patients (19.8%) showed relapse, and the recurrence rate was lower than that in the non-LT group (64.9%, 357/520, p < .001). Stratification analysis by American Joint Committee on Cancer (AJCC) stage showed that the stage I-II LT group had a lower recurrence rate than the non-LT group. Univariate comparative analysis demonstrated that multiplicity of tumor, tumor size, gross type, Edmondson- Steiner (ES) nuclear grade, extent of tumor, angioinvasion, AJCC stage, Milan criteria, University of California at San Francisco criteria on explant pathology (all p < .001), positive expression of cytokeratin 19 (p = .002), and preoperative α-fetoprotein (AFP) (p < .001) were predictors of tumor recurrence. In multivariate analysis, LT, preoperative AFP, multiplicity of tumor, extent of tumor, size of tumor, and ES nuclear grade were independent prognostic factors. Conclusions: LT might have a protective effect against the late recurrence of stage I-II HCC compared to non-LT, and the prognostic factors for recurrence were similar to previously well-known prognostic factors for HCC. -
Citations
Citations to this article as recorded by- Locoregional and Surgical Treatment of Single-Nodule Hepatocellular Carcinoma Recurrence After Liver Transplantation: A Systematic Review and a Meta-Analysis
Marco Maria Pascale, Camilla Marandola, Francesco Frongillo, Erida Nure, Salvatore Agnes
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- SIRT7, H3K18ac, and ELK4 Immunohistochemical Expression in Hepatocellular Carcinoma
- Hye Seung Lee, Wonkyung Jung, Eunjung Lee, Hyeyoon Chang, Jin Hyuk Choi, Han Gyeom Kim, Aeree Kim, Baek-hui Kim
- J Pathol Transl Med. 2016;50(5):337-344. Published online August 5, 2016
- DOI: https://doi.org/10.4132/jptm.2016.05.20
- 12,382 View
- 167 Download
- 27 Web of Science
- 27 Crossref
-
Abstract
PDF
- Background
SIRT7 is one of the histone deacetylases and is NAD-dependent. It forms a complex with ETS-like transcription factor 4 (ELK4), which deacetylates H3K18ac and works as a transcriptional suppressor. Overexpression of SIRT7 and deacetylation of H3K18ac have been shown to be associated with aggressive clinical behavior in some cancers, including hepatocellular carcinoma (HCC). The present study investigated the immunohistochemical expression of SIRT7, H3K18ac, and ELK4 in hepatocellular carcinoma.
Methods
A total of 278 HCC patients were enrolled in this study. Tissue microarray blocks were made from existing paraffin-embedded blocks. Immunohistochemical expressions of SIRT7, H3K18ac and ELK4 were scored and analyzed.
Results
High SIRT7 (p = .034), high H3K18ac (p = .001), and low ELK4 (p = .021) groups were associated with poor outcomes. Age < 65 years (p = .028), tumor size ≥ 5 cm (p = .001), presence of vascular emboli (p = .003), involvement of surgical margin (p = .001), and high American Joint Committee on Cancer stage (III&V) (p < .001) were correlated with worse prognoses. In multivariate analysis, H3K18ac (p = .001) and ELK4 (p = .015) were the significant independent prognostic factors.
Conclusions
High SIRT7 expression with poor overall survival implies that deacetylation of H3K18ac contributes to progression of HCC. High H3K18ac expression with poor prognosis is predicted due to a compensation mechanism. In addition, high ELK4 expression with good prognosis suggests another role of ELK4 as a tumor suppressor beyond SIRT7’s helper. In conclusion, we could assume that the H3K18ac deacetylation pathway is influenced by many other factors. -
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- Nuclear Expression of Hepatitis B Virus X Protein Is Associated with Recurrence of Early-Stage Hepatocellular Carcinomas: Role of Viral Protein in Tumor Recurrence
- Jing Jin, Hae Yoen Jung, KyuHo Lee, Nam-Joon Yi, Kyung-Suk Suh, Ja-June Jang, Kyoung-Bun Lee
- J Pathol Transl Med. 2016;50(3):181-189. Published online April 17, 2016
- DOI: https://doi.org/10.4132/jptm.2016.03.18
- 19,889 View
- 103 Download
- 11 Web of Science
- 9 Crossref
-
Abstract
PDF
- Background
Hepatitis B virus (HBV) plays well-known roles in tumorigenesis of hepatocellular carcinoma (HCC) in infected patients. However, HBV-associated protein status in tumor tissues and the relevance to tumor behavior has not been reported. Our study aimed to examine the expression of HBV-associated proteins in HCC and adjacent nontumorous tissue and their clinicopathologic implication in HCC patients.
Methods
HBV surface antigen (HBsAg), HBV core antigen (HBcAg), and HBV X protein (HBx) were assessed in 328 HBV-associated HCCs and in 155 matched nontumorous tissues by immunohistochemistry staining.
Results
The positive rates of HBsAg and cytoplasmic HBx staining in tumor tissue were lower than those in nontumorous tissue (7.3% vs. 57.4%, p < .001; 43.4% vs. 81.3%, p < .001). Conversely, nuclear HBx was detected more frequently in tumors than in nontumorous tissue (52.1% vs. 30.3%, p < .001). HCCs expressing HBsAg, HBcAg, or cytoplasmic HBx had smaller size; lower Edmondson-Steiner (ES) nuclear grade, pT stage, and serum alpha-fetoprotein, and less angioinvasion than HCCs not expressing HBV-associated proteins. Exceptionally, nuclear HBx-positive HCCs showed higher ES nuclear grade and more frequent large-vessel invasion than did nuclear HBx-negative HCCs. In survival analysis, only nuclear HBx-positive HCCs had shorter disease-free survival than nuclear HBx-negative HCCs in pT1 and ES nuclear grade 1–2 HCC subgroup (median, 126 months vs. 35 months; p = .015).
Conclusions
Our data confirmed that expression of normal HBV-associated proteins generally decreases in tumor cells in comparison to nontumorous hepatocytes, with the exception of nuclear HBx, which suggests that nuclear HBx plays a role in recurrence of well-differentiated and early-stage HCCs. -
Citations
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- J Pathol Transl Med. 2016;50(1):52-57. Published online November 18, 2015
- DOI: https://doi.org/10.4132/jptm.2015.10.09
- 11,990 View
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Abstract
PDF
- Background
Increasing evidence has shown that tumor initiation and growth are nourished by a small subpopulation of cancer stem cells (CSCs) within the tumor mass. CSCs are posited to be responsible for tumor maintenance, growth, distant metastasis, and relapse after curative operation. We examined the expression of CSC markers in paraffin-embedded tissue sections of hepatocellular carcinoma (HCC) and correlated the results with clinicopathologic characteristics. Methods: Immunohistochemical staining for the markers believed to be expressed in the CSCs, including epithelial cell adhesion molecule (EpCAM), keratin 19 (K19), CD133, and CD56, was performed in 82 HCC specimens. Results: EpCAM expression was observed in 56% of the HCCs (46/82) and K19 in 6% (5/82). EpCAM expression in HCC significantly correlated with elevated α-fetoprotein level, microvessel invasion of tumor cells, and high histologic grade. In addition, Ep- CAM expression significantly correlated with K19 expression. The overall survival and relapsefree survival rates in patients with EpCAM-expressing HCC were relatively lower than those in patients with EpCAM-negative HCC. All but two of the 82 HCCs were negative for CD133 and CD56, respectively. Conclusions: Our results suggest that HCCs expressing EpCAM are associated with unfavorable prognostic factors and have a more aggressive clinical course than those not expressing EpCAM. Further, the expression of either CD133 or CD56 in paraffin-embedded HCC tissues appears to be rare. -
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Abstract
PDF
- Background
There is increasing interest in hepatocellular carcinomas (HCC) expressing “stemness”-related markers, as they have been associated with aggressive behavior and poor prognosis. In this study, we investigated the usefulness of Sal-like protein 4 (SALL4), a recently proposed candidate marker of “stemness.” Methods: Immunohistochemical stains were performed for SALL4, K19, and epithelial cellular adhesion molecule (EpCAM) on tissue microarrays constructed from 190 surgically resected HCCs, and the results were correlated with the clinicopathological features and patient survival data. Results: Nuclear SALL4 expression was observed in 39/190 HCCs (20.5%), while K19 and EpCAM were expressed in 30 (15.9%) and 92 (48.7%) HCCs, respectively. The nuclear expression was generally weak, punctate or clumped. SALL4 expression was significantly associated with a poor overall survival compared to SALL4-negative HCCs (p = .014) compared to SALL4-negative HCCs. On multivariate analysis adjusted for tumor size, multiplicity, vascular invasion, and pathological tumor stage, SALL4 remained as a significant independent predictor of decreased overall survival (p= .004). SALL4 expression was positively correlated with EpCAM expression (p = .013) but not with K19 expression. HCCs that expressed both SALL4 and EpCAM were associated with significantly decreased overall survival, compared to those cases which were negative for both of these markers (p = .031). Conclusions: Although SALL4 expression was not significantly correlated with other clinicopathological parameters suggestive of tumor aggressiveness, SALL4 expression was an independent predictor of poor overall survival in human HCCs, and was also positively correlated with EpCAM expression. -
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Review
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- DOI: https://doi.org/10.4132/jptm.2015.04.15
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Abstract
PDF
- Understanding the important alterations during hepatocarcinogenesis as well as the characteristic magnetic resonance imaging (MRI) and histopathological features will be helpful for managing patients with chronic liver disease and hepatocellular carcinoma. Recent advances in MRI techniques, such as fat/iron quantification, diffusion-weighted images, and gadoxetic acid-enhanced MRI, have greatly enhanced our understanding of hepatocarcinogenesis.
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Original Article
- Overexpression of C-reactive Protein as a Poor Prognostic Marker of Resectable Hepatocellular Carcinomas
- Jin Ho Shin, Chong Jai Kim, Eun Jeong Jeon, Chang Ohk Sung, Hwa Jeong Shin, Jene Choi, Eunsil Yu
- J Pathol Transl Med. 2015;49(2):105-111. Published online March 12, 2015
- DOI: https://doi.org/10.4132/jptm.2015.01.19
- 13,413 View
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Abstract
PDF
- Background
C-reactive protein (CRP) is an acute phase reactant synthesized in the liver. CRP immunoreactivity is a feature of inflammatory hepatocellular adenomas with a higher risk of malignant transformation. A high serum CRP level denotes poor prognosis in hepatocellular carcinoma (HCC) patients. This study was conducted to determine whether CRP is produced in HCC and to assess the clinicopathologic significance of CRP expression in cancer cells. Methods: CRP immunoreactivity was examined in treatment-naïve HCCs (n=224) using tissue microarrays and was correlated with clinicopathologic parameters. The expression of CRP mRNA and protein was also assessed in 12 HCC cases by quantitative real-time polymerase chain reaction and immunoblotting. Hep3B and SNU-449 HCC cell lines were used for the analysis of CRP mRNA regulation by interleukin 6 (IL-6). Results: CRP was expressed in 133 of 224 HCCs (59.4%) with a variable degree of immunoreactivity (grade 1 in 25.9%; grade 2 in 20.1%; grade 3 in 13.4%). There was an inverse relationship between grade 3 CRP immunoreactivity and cancer-specific survival (p=.0047), while no associations were found with other parameters, including recurrence-free survival. The CRP mRNA expression level was significantly higher in CRP immunopositive cases than in immunonegative cases (p<.05). CRP mRNA expression was increased in Hep3B cells, but was not detected in SNU-449 cells even after IL-6 treatment. Conclusions: We report the expression of CRP in HCC for the first time. CRP expression was associated with poor cancer-specific survival in patients with resectable HCC. -
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Brief Case Reports
- Periductal Stromal Tumor of Breast: A Case Report and A Review of Literature
- Salma L. Abbasi, Kate McNamara, Mohammed S. Absar, Alison Darlington, Francene Clucas, Sami Titi
- Korean J Pathol. 2014;48(6):442-444. Published online December 31, 2014
- DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.6.442
- 13,618 View
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Gregor Krings, Gregory R. Bean, Elizabeth M. Hosfield, J Jordi Rowe, Joseph Geradts, Yunn-Yi Chen
Modern Pathology.2026; 39(3): 100961. CrossRef - Survey of recurrent diagnostic challenges in breast phyllodes tumours
Benjamin Yongcheng Tan, Stephen B Fox, Sunil R Lakhani, Puay Hoon Tan
Histopathology.2023; 82(1): 95. CrossRef - Management of a periductal stromal tumor in a young woman: Our breast unit experience
Irene Valente, Adela Ristani, Cristina Mancini, Eugenia Martella, Leonardo Quartieri, Cecilia D'Aloia
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Benjamin Yongcheng Tan, Puay Hoon Tan
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Kana TERAMOTO, Yasuro DOI, Kayo YAMAMOTO, Kaname MATSUKAWA, Hisaka IWAIHARA, Rumi MOTOSHIMA, Noboru TAKATA, Ichiro YOSHINAKA, Kazunori HARADA
Choonpa Igaku.2018; 45(1): 61. CrossRef
- Genetic Profiling of Mammary Periductal Stromal Tumors With Histologic Correlation Highlights High-Grade and Low-Grade Groups and Similarities to Phyllodes Tumors
- Solid Form of Epithelioid Hemangioma: A Case Report
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- DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.5.394
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Original Articles
- Histologic Disorderliness in the Arrangement of Tumor Cells as an Objective Measure of Tumor Differentiation
- Sungwook Suh, Gyeongsin Park, Young Sub Lee, Yosep Chong, Youn Soo Lee, Yeong Jin Choi
- Korean J Pathol. 2014;48(5):339-345. Published online October 27, 2014
- DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.5.339
- 7,676 View
- 66 Download
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Abstract
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- Background: Inter-observer and intra-observer variation in histologic tumor grading are well documented. To determine whether histologic disorderliness in the arrangement of tumor cells may serve as an objective criterion for grading, we tested the hypothesis the degree of disorderliness is related to the degree of tumor differentiation on which tumor grading is primarily based. Methods: Borrowing from the statistical thermodynamic definition of entropy, we defined a novel mathematical formula to compute the relative degree of histologic disorderliness of tumor cells. We then analyzed a total of 51 photomicrographs of normal colorectal mucosa and colorectal adenocarcinoma with varying degrees of differentiation using our formula. Results: A one-way analysis of variance followed by post hoc pairwise comparisons using Bonferroni correction indicated that the mean disorderliness score was the lowest for the normal colorectal mucosa and increased with decreasing tumor differentiation. Conclusions: Disorderliness, a pathologic feature of malignant tumors that originate from highly organized structures is useful as an objective tumor grading proxy in the field of digital pathology.
- Prognostic Significance of BCL9 Expression in Hepatocellular Carcinoma
- Jiyeon Hyeon, Soomin Ahn, Jae Jun Lee, Dae Hyun Song, Cheol-Keun Park
- Korean J Pathol. 2013;47(2):130-136. Published online April 24, 2013
- DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.130
- 9,652 View
- 71 Download
- 19 Crossref
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Abstract
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Background BCL9 enhances β-catenin-mediated transcriptional activity regardless of the mutational status of the Wnt signaling components and increases the cell proliferation, migration, invasion, and metastatic potential of tumor cells. The goal of this study was to elucidate the prognostic significance of BCL9 protein expression in hepatocellular carcinoma (HCC) patients.
Methods We evaluated BCL9 protein expression by immunohistochemistry in tumor tissue from 288 primary HCC patients who underwent curative hepatectomy. The impact of BCL9 expression on the survival of the patients was analyzed. The median follow-up period was 97.1 months.
Results Nuclear BCL9 protein expression was observed in 74 (25.7%) of the 288 HCCs. BCL9 expression was significantly associated with younger age (p=0.038), higher Edmondson grade (p=0.001), microvascular invasion (p=0.013), and intrahepatic metastasis (p=0.017). Based on univariate analyses, BCL9 expression showed an unfavorable influence on both disease-free survival (DFS, p=0.012) and disease-specific survival (DSS, p=0.032). Multivariate analyses revealed that higher Barcelona Clinic Liver Cancer stage was an independent predictor of both shorter DFS (p<0.001) and shorter DSS (p<0.001). BCL9 expression tended to be an independent predictor of shorter DFS (p=0.078).
Conclusions BCL9 protein expression might be a marker of shorter DFS in HCC patients after curative hepatectomy.
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Minjie Wu, Heng Dong, Chao Xu, Mengqing Sun, Haojin Gao, Fangtian Bu, Jianxiang Chen
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Kwang-Hoon Chun
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Roland Kotolloshi, Mieczyslaw Gajda, Marc-Oliver Grimm, Daniel Steinbach
International Journal of Molecular Sciences.2022; 23(10): 5319. CrossRef - Bcl9 Depletion Modulates Endothelial Cell in Tumor Immune Microenvironment in Colorectal Cancer Tumor
Zhuang Wei, Mei Feng, Zhongen Wu, Shuru Shen, Di Zhu
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Ivana Samaržija
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- CHD1L Is a Marker for Poor Prognosis of Hepatocellular Carcinoma after Surgical Resection
- Jiyeon Hyeon, Soomin Ahn, Cheol-Keun Park
- Korean J Pathol. 2013;47(1):9-15. Published online February 25, 2013
- DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.1.9
- 9,486 View
- 71 Download
- 24 Crossref
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Abstract
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Background The gene for chromodomain helicase/ATPase DNA binding protein 1-like (
CHD1L ) was recently identified as a target oncogene within the 1q21 amplicon, which occurs in 46% to 86% of primary hepatocellular carcinoma (HCC) cases. However, the prognostic significance of CHD1L in HCC remains uncertain. In this study, we investigated the roles of CHD1L in the prognosis of HCC.Methods We investigated the expressions of CHD1L in tumor tissue microarrays of 281 primary HCC patients who underwent surgical resection using immunohistochemistry. Prognostic factors of HCC were examined by univariate and multivariate analyses. The median follow-up period was 75.6 months.
Results CHD1L expression was observed in 48 of the 281 HCCs (17.1%). CHD1L expression was associated with a younger age (p=0.033), higher Edmondson grade (p=0.019), microvascular invasion (p<0.001), major portal vein invasion (p=0.037), higher American Joint Committee on Cancer T stage (p=0.001), lower albumin level (p=0.047), and higher α-fetoprotein level (p=0.002). Multivariate analyses revealed that CHD1L expression (p=0.027), Edmondson grade III (p=0.034), and higher Barcelona Clinic Liver Cancer stage (p<0.001) were independent predictors of shorter disease-free survival.
Conclusions CHD1L expression might be a prognostic marker of shorter disease-free survival in HCC patients after surgical resection.
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- The Histologic Cut-off Point for Adjacent and Remote Non-neoplastic Liver Parenchyma of Hepatocellular Carcinoma in Chronic Hepatitis B Patients
- Hae Yoen Jung, Soo Hee Kim, Jin Jing, Jae Moon Gwak, Chul Ju Han, Ja-June Jang, Kyoung-Bun Lee
- Korean J Pathol. 2012;46(4):349-358. Published online August 23, 2012
- DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.4.349
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- 56 Download
- 8 Crossref
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Abstract
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Background The molecular profile of peritumoral non-neoplastic liver parenchyma (PNLP) has recently been suggested as predictive factor of early and late recurrence of hepatocellular carcinoma (HCC). However, there is no definite cut-off point for tumor-free PNLP in terms of either histological or molecular changes. Therefore, our aim is to determine the numerical cut-off point for separating adjacent PNLP and remote PNLP in histopathologic perspective.
Methods Peritumoral tissues from 20 resected HCC patients were sampled from 0 to 40 mm distance from the tumor border (divided into 5-mm columns). Histopathologic parameters such as necroinflammatory activity, fibrosis, bile ductular reaction, hepatic venulitis, peliosis, and steatosis were compared between each column.
Results The morphologic changes just adjacent to the tumor were notably severe and faded with distance. The parenchyma within 10 mm of the tumor showed significantly severe inflammation, fibrosis, peliosis and hepatic venulitis compared with those from farther areas. The histopathologic changes of the parenchyma became stable beyond 20 mm.
Conclusions Results of this study revealed that the parenchyma within 10 mm distance from the tumor, or adjacent PNLP, has histopathologic changes that are directly affected by the tumor, and the parenchyma beyond 20 mm as the remote PNLP without tumor effect.
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Haiqing Wang, Aixiang Liu, Wentao Bo, Xielin Feng, Yong Hu, Lang Tian, Hui Zhang, Xiaoli Tang, Lixia Zhang
BioMed Research International.2018; 2018: 1. CrossRef - Forns index predicts recurrence and death in patients with hepatitis B‐related hepatocellular carcinoma after curative resection
Won‐Mook Choi, Jeong‐Hoon Lee, Hongkeun Ahn, Hyeki Cho, Young Youn Cho, Minjong Lee, Jeong‐ju Yoo, Yuri Cho, Dong Hyeon Lee, Yun Bin Lee, Eun Ju Cho, Su Jong Yu, Nam‐Joon Yi, Kwang‐Woong Lee, Yoon Jun Kim, Jung‐Hwan Yoon, Kyung‐Suk Suh, Chung Yong Kim, Hy
Liver International.2015; 35(8): 1992. CrossRef - Renal Histologic Parameters Influencing Postoperative Renal Function in Renal Cell Carcinoma Patients
Myoung Ju Koh, Beom Jin Lim, Kyu Hun Choi, Yon Hee Kim, Hyeon Joo Jeong
Korean Journal of Pathology.2013; 47(6): 557. CrossRef
- Does very high alpha-fetoprotein affect very early hepatocellular carcinoma receiving hepatectomy?
- Fine Needle Aspiration Cytology of hepatocellular Carcinoma: A Study on 247 Cases.
- Kwang Gil Lee, Jong Tae Lee, Soo Im Choi, Chan II Park
- J Pathol Transl Med. 1990;1(1):1-17.
- 42,719 View
- 91 Download
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Abstract
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- Hepatocellular carcinoma(HCC) is malignant tumor frequently occurring in Koreans. There have been few reports regarding the cytologic findings of fine needle aspiration(FNA) of HCC. Most have suggested a diagnostic problem in the cytology distinguishing HCC from some benign hepatic lesion-for example, a regeneration nodule in cirrhosis and liver cell adenoma. In spite of its high frequency in Korea, no cytologic study has been reported, concerning the FNA of HCC. In an attempt to achieve cytologic criteria for the diagnosis of HCC, the authors studied retrospectively cytopathologic findings of 247 cases of HCC. These cases were confirmed either by histologic examination including lobectomy, biopsy, or cell block material, or, when tissue diagnosis was unavailable, by a high serum alpha-fetoprotein level(over 400 I. U.). All aspiration smears were stained by the Papainicolaou method. In each case, the smears were analyzed for cell patterns and various cytomorphology of the tumor cells. The smear background was assessed for the presence of tumor cell necrosis and inflammatory components and compared to that of metastatic carcinomas. The cell patterns were classified as trabecular, acinar, dispersed, and irregular. The cytologic parameters analyzed included the degree of nuclear atypia and the presence of mitoses, intranuclear cytoplasmic inclusions, nucleolar prominency, endothelial lining, multinucleated giant cells, eosinophilc, globules bile and Mallory body. Most of the FNA of HCC showed markedly cellular smears. The tumor cells were most frequently arranged in a trabecular pattern(80.3%). The irregular(12.6%), the acinar(5.5%), and the dispersed patterns(1.7%) followed in decreasing frequency. Individual hepatoma cells were larger than normal liver cells. However, they had morphologic features characteristic of the hepatic cells : the cells were round or polygonal, their cytoplasm was abundant and granular with eosinophilic or amphophilic stainability, and their nuclei were round to oval, located centrally, and tended to have prominent nucleoli. Anaplasia and pleomorphism of tumor cells were generally mild to moderate. These findings existed even in very well differentiated cases. Mitotic figures were present in about 85% of the cases. Prominent nucleoli were observed only in about half the cases. The frequency of other cytologic features was as follows : intranuclear cytoplasmic inclusion in 86.8% ; endothelial lining in 56.1% ; bile in 19.8% ; and giant cells in 60.1%. Clear cells were often present in 11.7%, Most aspiration smears of HCC displayed clean background without necrosis or inflammatory material in contrast to the dirty, necrotic background of metastatic cancers and cholangiocarcinomas. Based on the above mentioned features, it is suqqested that the cytologic critieria most important for the diagnosis of HCC include a markedly cellular smear, trabecular pattern. hepatocytoid appearance of tumor cells, endothelial lining, the presence of bile, giant cells, intranuclear cytoplasmic inclusions, and prominent nucleoli, Among these, trabecular pattern, endothelial lining, giant cells and clean smear background are points to be considered in differentiating HCC from metastatic and cholangiocellular carcinoma.
- Fine Needle Aspiration Cytology of Hepatoblastoma: Report of Two Cases.
- Young Nyun Park, Kwang Gil Lee, Chan II Park
- J Pathol Transl Med. 1990;1(1):98-102.
- 2,178 View
- 35 Download
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Abstract
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- Hepatoblastoma(HB) is a rare embryonic malignant tumor of the liver. Most morphological studies on HB have limited to the histological characteristics and only 3 cases of HB have been described in the cytology literature. We present 2 cases of HB occurring in children aged 1 year and 3 years, respectively. The distinctive cytologic features of fine needle aspiration of HB were clusters of tumor cells showing acinar and trabecular pattern, smaller tumor cells with a high nuclear-cytoplasmic ratio and hyperchromatic nuclei having prominent nucleoli, and the presence of extramedullary hematopoiesis and osteoid material. These features were also found in the cell block and the biopsy specimen, and appeared very useful in the differentiation of HB from hepatocellular carcinoma.
- Expression of Multidrug Resistance Protein 1 in Human Hepatocellular Carcinoma.
- Yun Kyung Kang
- Korean J Pathol. 2011;45(3):281-289.
- DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.3.281
- 4,521 View
- 28 Download
- 1 Crossref
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Abstract
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- BACKGROUND
Multidrug resistance protein 1 (MDR1) encoded by ATP-binding cassette, sub-family B (Mdr/Tap), member 1 (ABCB1) mediates cross-resistance to antineoplastic drugs, and its expression is related to tumor aggressiveness.
METHODS
MDR1 expression was investigated in 100 hepatocellular carcinomas (HCCs) by immunohistochemical staining. The epigenetic mechanisms underlying ABCB1 transcriptional regulation were investigated in cell lines.
RESULTS
MDR1 was normally localized in the bile canalicular surface of the hepatocytes. Among 100 HCCs, 45 showed canalicular/luminal (CL) staining similar to the normal pattern, another 45 displayed membranous/cytoplasmic (MC) overexpression, and the remaining 10 revealed loss of expression. MC pattern or null staining of HCCs correlated with a higher histological grade and had a poorer prognosis than HCCs with a CL pattern (p<0.05). They also tended to have a poor prognosis by multivariate survival analysis. The ABCB1 promoter was hypomethylated regardless of MDR1 expression or ABCB1 mRNA levels in 10 HCC cell lines. Histone deacetylase inhibitor treatment induced ABCB1 upregulation in 4 cell lines with low or moderate ABCB1 levels.
CONCLUSIONS
Our findings suggest that either an increase or a loss of MDR1 expression may contribute to the poor outcome of HCCs; histone deacetylation may be one of the epigenetic mechanisms directing the ABCB1 expression in HCCs. -
Citations
Citations to this article as recorded by- Preferential expression of prostate specific membrane in CD34 labeled Neo-vasculature of Hepatocellular carcinoma: Prognostic and therapeutic potentials
Safaa MM Abd El Khalek, Mona QR Mohammed, Amira M Al Balakosy
Egyptian Journal of Pathology.2023; 43(1): 66. CrossRef
- Preferential expression of prostate specific membrane in CD34 labeled Neo-vasculature of Hepatocellular carcinoma: Prognostic and therapeutic potentials
Case Report
- Adrenal Cortical Adenoma Developed in Adrenohepatic Fusion, a Mimicry of Hepatocellular Carcinoma: A Case Report.
- Sun A Kim, Young Joo Lee, Kyoung Won Kim, Gyungyub Gong
- Korean J Pathol. 2011;45(2):196-200.
- DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.2.196
- 5,282 View
- 42 Download
- 4 Crossref
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Abstract
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- Adrenohepatic fusion is the union of the liver and adrenal gland with close intermingling of their respective parenchymal cells. Adrenal cortical adenoma arising in adrenohepatic fusion tissue is extremely rare, although adrenohepatic fusion itself is relatively common. Here we report a case of a 59-year-old man with a mass in the right lobe of his liver. The mass showed slight hyperattenuation during arterial phase and hypoattenuation during portal phase on dynamic computed tomography with contrast enhancement. On pathology, the mass consisted of round to polygonal cells with clear microvesicular or eosinophilic cytoplasm, arranged in nests or in a trabecular pattern. The tumor cells were positive for inhibin and melan-A, but negative for Hep Par-1. In the periphery of the mass, adrenohepatic fusion was identified between the liver and adrenal gland, and was simultaneously resected with the mass. We report this rare case, and discuss its clinical implications, especially the differential diagnosis with hepatocellular carcinoma.
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Citations
Citations to this article as recorded by- An intrahepatic adrenal adenoma mimicking hepatocellular carcinoma: A case report and literature review
Cheng-Ju Yang, Cheng-Ming Peng
Formosan Journal of Surgery.2025; 58(5): 222. CrossRef - Adrenal cortical adenoma arising in an adreno-hepatic fusion: Case report and literature review of a potential diagnostic pitfall
Adam Stenman, Ivan Shabo, Jan Zedenius, C. Christofer Juhlin
Human Pathology Reports.2022; 29: 300656. CrossRef - Intrahepatic adrenocortical adenoma arising from adrenohepatic fusion mimicking hepatic malignancy
Yong Soo Cho, Jin Woong Kim, Hyun Ju Seon, Ju-Yeon Cho, Jun-Hee Park, Hyung Joong Kim, Yoo Duk Choi, Young Hoe Hur
Medicine.2019; 98(23): e15901. CrossRef - Direct and indirect imaging features of adrenohepatic fusion
Jung Jae Park, Byung Kwan Park, Chan Kyo Kim
Abdominal Radiology.2016; 41(2): 377. CrossRef
- An intrahepatic adrenal adenoma mimicking hepatocellular carcinoma: A case report and literature review
Original Article
- The Expression of Apolipoprotein D in Hepatocellular Carcinoma.
- Hongxiu Han, Chan Kum Park
- Korean J Pathol. 2010;44(2):187-190.
- DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.2.187
- 3,787 View
- 27 Download
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Abstract
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- BACKGROUND
Apolipoprotein D (Apo D) has recently been identified as a novel tumor suppressor gene. Apo D may have a profound effect on the carcinogenesis and progression of hepatocellular carcinoma. This study was designed to evaluate the expression of Apo D in hepatocellular carcinoma and to investigate the relationship between the expression of Apo D and the clinicopathological characteristics and the patients' survival.
METHODS
An immunohistochemical study was performed on the tumors and tissues from 43 hepatocellular carcinoma (HCC) patients with controls to determine the expression of Apo D protein.
RESULTS
Our data showed that a higher expression of Apo D was seen in 10 of 43 cases (23.3%), while a lower and no expression of Apo D was observed in 28 of 43 cases (65.1%) and 5 of 43 cases (11.6%), respectively. A reduced expression of Apo D was correlated with the tumor stage (p = 0.037) and tumor size (p = 0.017). However, the patients' 5-year survival was not associated with the expression of Apo D (p = 0.903).
CONCLUSIONS
The results suggest that a reduced Apo D protein expression may play an important role in HCC progression as associated with the tumor stage and size, but it does not affect the survival of HCC patients.
Case Report
- Hepatoid Thymic Carcinoma: A Case Report.
- Jeong Hyeon Lee, Hyunchul Kim, Yang Seok Chae, Nam Hee Won, Jong Sang Choi, Chul Hwan Kim
- Korean J Pathol. 2009;43(6):562-565.
- DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.6.562
- 4,395 View
- 31 Download
- 1 Crossref
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Abstract
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- We report here on a rare case of hepatoid thymic carcinoma in a 34-year-old man. The patient complained of a high fever and headache, and a 6.6cm-sized anterior mediastinal mass was found on chest computed tomography (CT). There was no hepatic mass seen on abdominal CT. The resected mass consisted of epithelioid cells with abundant eosinophilic cytoplasm, pleomorphic vesicular nuclei and prominent nucleoli, and the mass was surrounded by thymic tissue. The tumor cells were immunopositive for cytokeratin 7, alpha-1-antitrypsin, hepatocyte staining, and epithelial membrane antigen, but they were negative for CD5, alpha-fetoprotein (AFP) and placental alkaline phosphatase, and this all led to a diagnosis of hepatoid thymic carcinoma rather than hepatoid yolk sac tumor. This entity should be included in the differential diagnosis of epithelioid thymic tumors.
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Citations
Citations to this article as recorded by- Hepatoid thymic carcinoma in a polycythemia vera patient treated with ropeginterferon Alfa-2b: Clinical, histopathological and molecular correlates
Giuseppe G. Loscocco, Margherita Vannucchi, Raffaella Santi, Andrea Amorosi, Stefania Scarpino, Maria Chiara Siciliano, Paola Guglielmelli, Claudio Tripodo, Arianna Di Napoli, Alessandro M. Vannucchi
Pathology - Research and Practice.2024; 263: 155648. CrossRef
- Hepatoid thymic carcinoma in a polycythemia vera patient treated with ropeginterferon Alfa-2b: Clinical, histopathological and molecular correlates
Original Articles
- Enhanced Protein Expression of Signal Transducer and Activator of Transcription 3 and Protein Kinase Substrate p36 in Hepatocellular Carcinoma.
- Hongxiu Han, Si Hyong Jang, Chan Kum Park
- Korean J Pathol. 2009;43(5):393-399.
- DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.5.393
- 3,561 View
- 28 Download
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Abstract
PDF
- BACKGROUND
Signal transducers and activators of transcription 3 (STAT3) and protein kinase substrate p36 may be involved in cell proliferation, differentiation and growth.
METHODS
Immunohistochemistry for STAT3 and p36 was performed in 46 patients with hepatocellular carcinoma (HCC).
RESULTS
STAT3 staining was present in the cytoplasm and/or nucleus, while p36 staining was present in the nucleus. STAT3 and p36 expression occurred in 78.3% (36/46) and 47.8% (22/46) of HCC patients, respectively. However, no correlation was found between STAT3 and p36 protein expression (p>0.05). Enhanced expression of STAT3 was negatively correlated with portal vein invasion (p=0.033). Expression of STAT3 in the nucleus was correlated with tumor grade (p=0.004). Enhanced expression of p36 was correlated with tumor grade (p=0.031). HCC was correlated with HBV infection (p=0.032). The patients'5-year survival was related to expression of p36 (p=0.044), but not to total STAT3 or nuclear STAT3 (p>0.05).
CONCLUSIONS
The enhanced expression of STAT3 in the nucleus and the enhanced expression of p36 are associated with the aggressive phenotype of HCC. Enhanced p36 expression may contribute to poor survival of patients with HCC.
- The Expressions of Nerve Growth Factor and Its Receptor p75NGFR in Hepatocellular Carcinoma: Their Relation with the Clinicopathologic Factors.
- Woo Sung Moon, Kyu Yun Jang, Myoung Ja Chung, Myoung Jae Kang, Dong Geun Lee, Ho Lee, Ho Sung Park
- Korean J Pathol. 2009;43(2):145-151.
- DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.2.145
- 4,885 View
- 24 Download
- 1 Crossref
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Abstract
PDF
- BACKGROUND
Nerve growth factor (NGF) has been suggested to participate in tumor progression and it can interact with its receptor p75NGFR. In the present study, we investigated the expressions of NGF and p75NGFR in hepatocellular carcinoma (HCC).
METHODS
We performed immunohistochemistry for NGF, p75NGFR and PCNA in 45 cases of HCCs, and examined the relationships between the clinicopathologic factors and the immunohistochemical results.
RESULTS
NGF was detected in 84.4% (38/45) of the tumor cells and in 64.4% (29/45) of the non-tumorous hepatocytes. Furthermore, a NGF expression was present in 28.9% (13/45) of the endothelial cells in the HCCs, but in 80% (36/45) of the endothelial cells in the non-tumor liver tissue. The tumor cells were negative for p75NGFR in all the HCCs. Although a p75NGFR expression was present in all the nerve fibers in the non-tumor liver tissues, it was markedly reduced (42.2%; 19/45) in the HCCs and a p75NGFR expression was observed at the sinusoids or around the large vessels. The HCCs expressing NGF, either in the tumor cells or the endothelial cells, showed a larger size than those HCCs that didn't express NGF. The NGF positive tumors showed a tendency toward a higher PCNA-labeling index than did the negative tumors.
CONCLUSIONS
The changed localization of the NGF expression and the decreased expression of p75NGFR are associated with hepatic carcinogenesis. We suggest that a NGF expression may contribute to the progression of HCC. -
Citations
Citations to this article as recorded by- Expression of nerve growth factor and heme oxygenase-1 predict poor survival of breast carcinoma patients
Sang Jae Noh, Jun Sang Bae, Urangoo Jamiyandorj, Ho Sung Park, Keun Sang Kwon, Sung Hoo Jung, Hyun Jo Youn, Ho Lee, Byung-Hyun Park, Myoung Ja Chung, Woo Sung Moon, Myoung Jae Kang, Kyu Yun Jang
BMC Cancer.2013;[Epub] CrossRef
- Expression of nerve growth factor and heme oxygenase-1 predict poor survival of breast carcinoma patients
Case Report
- Gastric Adenocarcinoma with Coexistent Hepatoid Adenocarcinoma and Neuroendocrine Carcinoma: A Case Report.
- Aeri Kim, Sang Woon Kim, Sun Kyo Song, Young Kyung Bae
- Korean J Pathol. 2009;43(1):79-82.
- DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.1.79
- 4,267 View
- 34 Download
- 2 Crossref
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Abstract
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- This report represents a very rare case of a gastric adenocarcinoma that was coexistent with hepatoid adenocarcinoma and neuroendocrine carcinoma. A 77-year-old man was admitted to our hospital due to a huge ulcerofungating mass identified at the proximal body of the stomach. After a pathological diagnosis of the tumor as a poorly differentiated adenocarcinoma was made, the patient underwent a total gastrectomy with lymph node dissection. Microscopically, the tumor consisted of three morphologically distinct components-tubular adenocarcinoma, hepatoid adenocarcinoma and neuroendocrine carcinoma. The hepatoid adenocarcinoma component resembled a hepatocellular carcinoma and produced alpha-fetoprotein. The neuroendocrine carcinoma component was positive for chromogranin and synaptophysin immunostains. This is an example of the diverse morphological and immunophenotypical differentiation of gastric carcinomas.
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Citations
Citations to this article as recorded by- An Intestinal Type Gastric Neuroendocrine Tumor: A Case Report
Mohammad Abu-Jeyyab, Renata Kakish, Malak Alkatib, Leen Alshawabkeh, Rawan Bani Hamad, Mary Almadani, Ma'wia Santarisi, Mohammad Al-Jafari, Abdulqadir J. Nashwan
Case Reports in Oncology.2023; 16(1): 1113. CrossRef - Gastric adenocarcinoma is concurrent with metastatic neuroendocrine cancer treated with nivolumab and chemotherapy: A case report
Bing Yan, Meiqi Cui, Junhao You, Fang Li, Hui Liu
Molecular and Clinical Oncology.2018;[Epub] CrossRef
- An Intestinal Type Gastric Neuroendocrine Tumor: A Case Report
Original Articles
- The Effects of Transforming Growth Factor beta1 on Apoptosis in Rat Hepatocellular Carcinoma.
- Young Euy Park, Young Hee Choi, Won Yo Lee, Jin Ja Park, Kyung Chan Choi, Hyung Shik Shin
- Korean J Pathol. 1999;33(2):71-79.
- 1,924 View
- 10 Download
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Abstract
- Based upon the concept that carcinogenesis is associated with apoptosis, specific therapies designed to enhance the susceptibility of cancer cells to undergo apoptosis could be developed. Thus, in this paper, it was designed to investigate whether, using rat animal model with chemical-induced hepatocellular carcinoma, TGF-1 in vivo could induce apoptosis in cancer. The chemical hepatocarcinogenic procedure of Solt-Farber method was used on Sprague-Dawley rats. Experimental groups were divided into group A treated with the standard Solt-Farber regimen of diethylnitrosamine (DEN) and 2-Acetaminofluorene (AAF), group B TGF-, group C TGF-1, and group D adriamycin after hepatocellular carcinoma developed. For detection of apoptotic cells, apoptotic indices were examined by the in situ end DNA labelling method. The expression of proliferating cell nuclear antigen was examined by immunohistochemical staining. Apoptosis of rat hepatocellular carcinoma cells increased significantly to 4.92+/-2.32/HPF in the group C compared with the control group (A) (2.54+/-1.13/HPF; P<0.05). Two distinctly different populations of proliferating hepatocellular carcinoma cells were identified. The cells at G1/S boundary (weak granular staining) increased to 15.75+/-6.19/HPF and 6.45+/-2.93/HPF in the groups C and D, respectively, but decreased to 2.42+/-2.06/HPF in the group B compared with the control group (A) (6.38+/-2.18/HPF; p<0.05). The cells at S phase (strong granular staining) increased to 3.37+/-2.69/HPF in the group B but decreased to 0.32+/-0.47/HPF in the group D (p<0.05). In conclusion, these results indicate that the TGF-1 may be used as an effective anticancer agent.
- Kupffer Cells in Hepatocellular Carcinoma.
- Young Nyun Park, Soon Hee Jung, Chan Il Park
- Korean J Pathol. 1989;23(3):305-310.
- 3,192 View
- 91 Download
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Abstract
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- Kupffer cells are tissue macrophages (histiocytes) fixed in hepatie sinusoids. Since malignant hepatocytes are the only tumor parencymal cells of the hepatocellular carcinoma, theoretically there are no Kupffer cells within the hepatocellular carcinoma. To clarify whether it is true or not, 12 cases of hepatocellular carcinoma of the trabecular type with some extents of the non-neoplastic surrounding liver were subjected to immunoperoxidase staining for lysozyme and S-100 protein and the results are as follows. 1) Kupffer cells were stained positively by the immunoperoxidase staining for lysozyme but not for S-100 protein, indicating that they are monocyte derived macrophages. 2) Kupffer cells were also present within the hepatocellular carcinoma, but were 2-7 times fewer within the hepatocellular carcinoma than in the non-neoplastic areas (p<0.05). 3) The non-neoplastic hepatic tissue of patients with serum HBsAg shows a tendency to have more kupffer cells than those without HBsAg.
- Clinicopathologic Features of Early Hepatocellular Carcinoma.
- Chang Ohk Sung, Suk Jin Choi, Cheol Keun Park
- Korean J Pathol. 2004;38(3):138-144.
- 2,483 View
- 23 Download
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Abstract
PDF
- BACKGROUND
Early hepatocellular carcinoma (HCC) is an early stage HCC, and it is sometimes difficult to identify the margins of the cancer nodules in the resected specimens.
METHODS
We studied 22 cases of early HCC to investigate the clinicopathologic features of early stage HCC.
RESULTS
Seven of 22 cases were single HCC, and 15 were multicentric HCC. The average tumor size was 1.34 cm (0.4-2.7 cm). Early HCCs didn't destroy the basic architecture of the liver lobules or pseudolobules and the lesions had an indistinct margin. Most tumors were uniformly composed of well-differentiated cancer tissue that was characterized by an increased cell density and an irregular thin-trabecular pattern. The tumor retained a varying number of portal tracts. There was a replacing growth pattern at the tumor-nontumor boundary without tumor capsule. Three of 22 cases had a "nodule-in-nodule" lesion, and the inner nodules consisted of moderately differentiated HCC without portal tracts. All 22 cases showed no vascular invasion. All 7 patients with single early HCC have survived for the past 11-54 months without any local recurrence. But in one patient with single early HCC, multicentric HCC developed 20 months after surgery.
CONCLUSION
The clinicopathologic features of early HCCs are quite different from those of advanced HCCs. The increased recognition of early HCC during routine clinical practice will contribute to improved patient survival.
- A Study on the Expression of Proliferating Cell Nuclear Antigen and Apoptosis of the Hepatocellular Carcinoma in Human and Hepatitis B Virus X Transgenic Mice.
- Hyung Bae Moon, Dae Yeul Yu, Hyung Ryun Yoo, Byung Joon So, Kwon Mook Chae, Haak Cheol Kim, Ki Jung Yun, Won Cheol Han, Hyang Jeong Jo, Bo Yong Kim
- Korean J Pathol. 2001;35(2):129-136.
- 2,075 View
- 19 Download
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Abstract
PDF
- BACKGROUND
This experiment was designed to study the cell kinetics of hepatocellular carcinoma (HCC) in both hepatitis B virus X (HBx) transgenic mice and humans.
METHODS
The immunohistochemical stain of proliferating cell nuclear antigen (PCNA) and TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay of apoptosis were used on formalin fixed-paraffin embedded tissues.
RESULTS
PCNA labeling indices (PCNA-LI) in the liver of HBx transgenic mice were markedly increased in HCC (11.3%) compare to the dysplastic areas (1.3%) and in the liver of non-transgenic littermates (0.1%). There was no significant difference of PCNA-LI in the dysplastic areas between HCC developed mice and non-HCC developed mice. Apoptosis labeling indices (Apoptosis-LI) in both the dysplastic areas and HCC of HBx transgenic mice were similar to those of non-transgenic littermates. PCNA-LI was markedly increased in human HCC (28.9%) compare to the background of HCC (2.9%) and the control liver (2.9%). Apoptosis-LI was decreased in human HCC (0.3%) compare to the background of HCC (0.4%) and the control liver (1.0%). Conclusion : There is a marked increase of cell proliferating activity in human HCC and in HCC of HBx transgenic mice, and there is a decrease of apoptosis in human HCC, but not in HCC of HBx transgenic mice.
- Cytologic Diagnosis of Metastatic Hepatocellular Carcinoma by Aspiration Cytology of Sacrum.
- Jungweon Shim, Illhyang Ko
- J Pathol Transl Med. 1990;1(2):179-184.
- 2,194 View
- 17 Download
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Abstract
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- Bone metastasis of hepatocellular carcinoma appears to be peculiar when clinical manifestation of liver disease is not apparent, and initial diagnosis of metastatic hepatocellular carcinoma by fine needle aspiration cytology is rarely obtained. We experienced a case of 45-year-old man with metastatic hepatocellular carcinoma in the sacrum, which was diagnosed by fine needle aspiration cytology. The intrahepatic mass, measuring 1.2 cm in diameter and kept unchanged in size for two years, was never proved to be hepatocellular carcinoma histopathologically. The aspirated neoplastic cells were mostly in sheets, showing abundant acidophilic cytoplasm and large, round. centrally located nuclei with single, prominent acidophilic mucleoti. In the cell block section, diagnosis of metastatic well-differentiated hepatocellular carcinoma was made without difficulty, and definite trabecular fashion with sinusoidal endothelial cell lining was found.
- Rarity of EGFR and c-ErbB-2 Overexpressions in Hepatocellular Carcinoma: An Immunohistochemical Study.
- Woo Sung Moon, Hyun Jin Son, Ho Sung Park, Min Young Park
- Korean J Pathol. 2004;38(4):244-248.
- 2,337 View
- 13 Download
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Abstract
PDF
- BACKGROUND
The overexpression of epidermal growth factor receptor (EGFR) and c-erbB-2 oncogenes has been implicated in the development of many types of cancer. However, the role of EGFR and c-erbB-2 overexpression in hepatocellular carcinoma (HCC) has not been fully elucidated.
METHODS
The aim of this study was to evaluate the immunohistochemical expression of EGFR and c-erbB-2 oncoprotein in a series of 52 HCCs.
RESULTS
All but one of the HCC tumor tissues were negative for EGFR monoclonal antibody, clone H11. All of the HCC tumor tissue samples were negative for EGFR monoclonal antibody, clone 29.1.1. However, strong EGFR immunoreactivity was detected in sinusoidal endothelial cells of HCC in 25 tumors (48%) using EGFR 29.1.1 antibody. The expression of c-erbB-2 was observed in 6% (3/52) of the HCCs. No significant correlation was found between p53 mutation and the expression of c-erbB-2.
CONCLUSION
Our results suggest that both EGFR and c-erbB-2 oncoprotein overexpressions in tumor cells are rare and do not seem to predominantly contribute to the malignant phenotype in HCC.
- Immunohistochemical Localization of Extracellular Matrix Components in Diabetic Nephropathy.
- Seung Sam Paik, Moon Hyang Park
- Korean J Pathol. 1997;31(5):427-435.
- 1,986 View
- 19 Download
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Abstract
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- Normal human glomerular basement membrane (GBM) and mesangial matrix (MM) contain several different basement membrane components in varying degrees. The characteristic morphological and ultrastructural changes in patients with diabetic nephropathy are the thickening of the GBM and the expansion of the MM. In order to investigate the changes of extracellular matrix components in diabetes, the immunohistochemical localization was performed in 17 cases with different degrees using antisera to human collagen types I, III, IV, VI, fibronectin, and laminin. The following results were obtained: 1. The reactivity for collagen IV was increased in expanded MM in the diffuse glomerulosclerosis (GS). With the progression to the nodule formation, collagen IV was prominently decreased in the peripheral area of the nodules. 2. Collagen VI was increased in GBM and MM in the diffuse GS, it was especially prominent in the expanded MM. With the progression to nodule formation, collagen VI was prominently increased in the periphery of the nodules. 3. Interstitial collagen I and III were not stained in many of the cases with the diffuse GS. With the progression to nodule formation, these were slightly expressed. A lamellar pattern of positive reaction was noted at the periphery of the late nodular lesions. 4. Fibronectin was increased in GBM & MM in the diffuse GS, it was especially intense in the MM. With the progression to the nodule formation, the reactivity of antibody to the fibronectin was decreased. 5. Laminin was weakly stained along the GBM & trace in the MM, but was not changed in the nodular GS. In summary, the expanded mesangial matrix in the diffuse GS showed a markedly increased staining for collagen IV, fibronectin and collagen VI. Less intense linear staining for collagen VI, fibronectin, laminin, collagen IV and collagen III was noted along the GBM. In the nodular GS, the composition of the early nodules resembled that of the diffuse GS. However, the late nodular lesion of the nodular GS revealed decreased reactivity for collagen IV and fibronectin at the periphery of the nodule, where collagen VI and interstitial collagen I and III were increased in laminated pattern.
- Analysis of DNA Ploidy Patterns and Nuclear Morphometry in Diethylnitrosamine Induced Hepatocyte Nodules and Hepatocellular Carcinoma of Rats.
- Chan Choi, Myung Kwan Kim, Kwan Mook Chae, Eun Cheol Kim, Hyung Bae Moon
- Korean J Pathol. 1993;27(3):226-234.
- 2,328 View
- 24 Download
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Abstract
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- This study was designed to answer the question; (1) How does the DNA ploidy pattern change in hepatocarcinogenesis? (2) How does the nuclear morphology change in hepatocarcinogenesis? Diethylnitrosamine(DEN) (16.5 mg per kg) was subcutaneously injected to female Sprague-Dawley rats(150~200g) by weekly interval for 30 weeks. DNA ploidy and parameters of nuclear morphology were measured by image analyser(IBAS 200, Kontron, FRG). The DNA ploidy pattern was divided into three basic patterns(diploid, polyploid, and aneuploid modes). In 8 cases of saline-injected control rats, the DNA histograms showed all polyploid pattern. Inhepatocyte nodules(hyperplastic nodules), DNA diploidy was the most frequent pattern, being followed by polyploid and aneuploid DNA patterns, contrast to hepatocelular carcinomas in which polyploid DNA pattern was most frequently noted being followed by diploid and aneuploid DNA pattern. Although the nuclei of hepatocytes in hepatocyte nodules and hepatocellular carcinomas were larger and more pleomorphic than those of normal hepatocytes, they were as same as those of normal hepatocytes in regard to nuclear hyperchromasia. DNA content, which was increased in hepatocarcinogenesis, was significantly related to the nuclear area.
- Expression of Fas/Fas Ligand and Its Relationship with Apoptosis in Chemically Induced Preneoplastic Lesions in Rat Liver.
- Hye Jin Lee, Do Youn Park, Kyung Un Choi, Jee Yeon Kim, Chang Hun Lee, Mee Young Sol, Kang Suek Suh
- Korean J Pathol. 2001;35(5):383-390.
- 2,124 View
- 15 Download
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- BACKGROUND
Apoptosis of hepatocytes plays a major role in experimental hepatocarcinogenesis of rats. But sequential change and localization of Fas and Fas ligand (FasL) in preneoplastic lesions and the relationship with apoptosis are not clearly elucidated.
METHODS
We investigated sequential change and localization of Fas/FasL and its relationship to apoptosis in preneoplastic lesions of chemical hepatocarcinogenesis in rats using northern blot analysis, immunohistochemistry and terminal deoxynucleotidyl transferase end labeling (TUNEL) assay.
RESULTS
We found that mRNA of Fas and Fas ligand increased for up to 42 days and 14 days after partial hepatectomy, respectively, and thereafter decreased with time. Fas protein was localized on the cytoplasm of hepatocytes of preneoplastic lesions, as well as on the cytoplasmic membrane of the adjacent liver parenchyme. Fas negative preneoplastic lesions were evident at 42 days after partial hepatectomy. FasL protein was found only in the cytoplasm of hepatocytes of preneoplastic lesions, instead of in the adjacent liver parenchyme. FasL-positive hepatocytes increased with time for up to 14 days after partial hepatectomy and therafter decreased. Also, TUNEL-positive apoptotic cells increased with time and were more numerous in the adjacent liver parenchyme than in the preneoplastic lesions.
CONCLUSIONS
It was suggested that Fas/FasL-mediated apoptosis might be one of the major mechanisms for controlling apoptotic cell death in the promotion stage of chemical hepatocarcinogenesis.
- Immunohistochemical Study of the Expression of p53, Pan-ras, c-erbB-2 and PCNA in N-Nitrosomorpholine(NNM)-Induced Hepatocellular Carcinoma of Rats.
- Ok Kyung Kim, Ryun Jo Shin
- Korean J Pathol. 1995;29(6):727-739.
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- The focus of this study was o aialyze the morphologic expression of p53, Pan-ras, c-erbB-2, and PCNA in preneoplastic and neoplastic liver lesions induced with NNM of rats. The development of hepatocellular tumors was investigated by histology and electron microscope in 65 Splague-Dawley rats administered with NNM in drinking water at low dose(5 mg/100 ml) and high dose(20 mg/100 ml). Three types of hepatocytic degeneration glycogenotic, eosinophilic and basophilic changes were followed by the appearance of hepatocellullar carcinoma. Hepatocellular carcinoma was increased in number and size according to NNM dosage and to duration of exposure. The histological classifications of hepatocelular carcinoma wer trabecular type, which was which was the most common, large eosinophilic, small cell, adenocarcinomatous and clear cell type. The expression of p53, Pan-ras, c-erbB-2 PCNA was examined by immunohistochemical stains. Eosinophilic degeneration revealed mild positivity at 18-26 weeks for expression of all oncogenic proteins studied and PCNA, whereas precancerous lesions showed variable expression from negative to moderate positivity on PCNA. Hepatocellular carcinoma lesions showed strong positivity for all stains and increased intensity during experimental period. These may indicate that chemical carcinogen produce hepatic eosinophilic degeneration and preCancerOus lesions by genetic mutation, resulting in hepatocellular carcinoma.
- The Tissue Expression of HBsAg and HBcAg in Hepatocellular Carcinoma and Peritumoral Liver.
- Jee Young Han, Woo Hee Jung, Chae Yoon Chon, Chan Il Park
- Korean J Pathol. 1993;27(4):371-378.
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- To evaluate the tissue expression rate and pattenr of HBsAg and HBcAg in tumors and peritumoral livers, an immunohistochemical study was undertaken on 47 surgically resected hepatocellular carcinomas(HCCs). The results are as follows. 1. Patient's sera were positive for HBsAg in 40 cases(85.1%). In the remaining 7 cases, the tumor and peritumoral liver expressed neither HBcAg nor HbSaG, suggesting that they were caused by other etiologies than hepatitis B virus. 2. The peritumoral liver had HBsAg and HBcAg in 95.0% and 27.5% among the 40 cases, respectively. But the tumor expressed HBsAg in 50.0% and HBcAg in none. 3. The expression of HBsAg within the tumor and both HBsAg and HBcAg in the peritumoral liver tended to be more frequent in the pretreated cases before surgery. 4. Edmondson-Steiner grade IV tumors revealed a lower expression rate of HBsAg than the low grade tumors(p<0.05). Incases with cirrhosis at peritumoral tissues, HBcAg was less frequently found than in those without cirrhosis. The majority of tissue HBsAg and HBcAg was represented as groups of positive cells. These results suggest that, during the development and progression of HCCs, the HBcAg containing cells are repeatedly removed and the HBcAg negative cells are selected, because cellular expression of HBcAg is the target of host immune response.
- Expression of ICAM-1 on Short-Term Cultured Human Keratinocytes: Modulation by IFN-gamma, UVB and retinoic acid.
- Bang Hur, Duck Ha Kim, Man Ha Hur
- Korean J Pathol. 1995;29(6):746-755.
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Abstract
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- Intercellular adhesion molecule I(ICAM-1; CD 54), a 90 kD glycoprotein, counter-receptor for lymphocyte function-associated antigen-I(LFA-1) on T-cells, is critically important to a wide variety of adhesion-dependent leukocyte functions, including antigen presentation and target cell lysis. Induction of ICAM-1 on the keratinocytes(KCs) is an important regulator in initiation, maintenance, and resolution of cutaneous inflammation, which is modulated with cytokines produced by activated T-lymphocytes. This study was designed to further our understanding on modulation effects of ultraviolet B(UVB), gamma interferon(IFN-;v), and retinoic acid(all trans) upon expression of ICAM-1 on cultured human KCs, with emphasis on their correlation. Cell surface expression of ICAM-1 in cultured human KCs was analyzed with the use of indirect immunofluorescence and fluorescence activating cell sorting(FACS) by flow cytometry. The results of this study were as follows: 1) Expression of ICAM-1 was significantly induced with IFN-,-(20 U/ml)(p<0.005). 2) UVB irradiation of 30mJ/cm2 significantly suppressed ICAM-1 expression of KCs 24 hours after irradiation(p<0.05). However, at 72 hours after irradiation, ICAM-1 expression of KCs was considerably increased in comparison to that of initial phase (24 hours after irradiation). 3) High concentrations(10(-5)M) of retinoic acid reduced UVB-induced expression of ICAM-1 in late phase(72 hours after irradiation), although retinoic acid showed induction effect of ICAM- I expression of KCs. In summary, these results indicate that ICAM- I may contribute to the biphasic effect of UVB on delayed hypersensitivity in vivo. Also, retinoic acid, a vitamin A derivative, may have a cutaneous photoprotective effect through a regulation of UVB-induced ICAM-1 expression on the KCs.
Case Report
- Cellular Schwannoma Arising in a Facial Nerve.
- Mee Joo, Hye Sung Kim, Yun Kyung Kang, Hye Kyung Lee, Jae Young Park
- Korean J Pathol. 1997;31(7):688-691.
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- Cellular schwaninoma is a variant of schwannoma, which is characterized by predominance of cellular Antoni A area, presence of mitotic activity, nuclear hyperchromasia, pleomorphism, and absence of Verocay body. These pathologic features often prompted a misdiagnosis of malignancy. However, the clinical outcome has indicated the benignity of the tumor. We have experienced a case of cellular schwannoma arising from right facial nerve with right hemifacial weakness and erosion of mastoid process. Grossly, it was a 3.5 x 3 cm sized and relatively well encapsulated mass with yellowish, friable cut surface. Microscopically, cellular growth with moderate cellular pleomorphism and some mitotic activity (5/40 HPFS, up to 2/HPF) were noted. Immunostaining for S-100 protein showed diffuse strong positive reaction.
Original Article
- Relationship between Proliferative Activity and Expression of HBcAg and p53 Protein in Hepatocellular Carcinoma and Surrounding Nontumorous Liver.
- So Ya Paik, Ho Guen Kim, Chan Il Park
- Korean J Pathol. 1997;31(8):773-781.
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- In an attempt to discover the factors contributing to the increased proliferative activity in hepatocytes and subsequent development of HCC, the proliferative activity of hepatocytes was compared with the size of regenerative nodules and HBcAg expression status in the surrounding nontumorous liver of 45 surgically resected hepatocellular carcinomas, including 34 HBV related ones. In the tumor, the difference in proliferative activity and the histological grade was analyzed in terms of p53 gene alteration. The proliferative activity was assessed by immunohistochemical methods using Ki-67 monoclonal antibody. HBcAg expression in the surrounding nontumorous liver correlated with both the inflammatory and proliferative activity of hepatocytes (p<0.05). p53 overexpression was associated with high proliferative activity and aggressive phenotype of tumor. No correlation was observed between the proliferative activity of hepatocytes and the size of regenerative nodules in cirrhosis (p>0.05). p53 overexpression was not evident in surrounding nontumorous liver including cirrhosis. In conclusion, the above results are in line with the view that hepatic carcinogenesis is a mutistep, progressive process. In the initial stage, chronic cellular injury incurred by immumologic reaction against HBcAg seems to play a pivotal role in increased cellular regeneration. However, once transformation of hepatocytes occur the major contributor to tumor growth seems to be alteration in p53 tumor suppresor gene.
Case Report
- A Case of Combined Hepatocellular and Cholangiocarcinoma with Neuroendocrine Differentiation and Sarcomatoid Transformation: A Case Report.
- Mi Jung Kim, Hyun Lyoung Koo, Seung Kyu Lee, Jae Y Ro, Eunsil Yu
- Korean J Pathol. 2005;39(2):125-129.
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- We report here on a case of combined hepatocellular and cholangiocarcinoma (CHC) with neuroendocrine differentiation and sarcomatoid transformation. A 59-year-old male who had had HBV-associated chronic liver disease presented with hepatic masses. The explanted liver showed three small masses, two in the right lobe and one in the left lobe. The largest one in the right lobe was a 2.0 cm sized binodular mass,consisting of a yellowish tan nodule and an abutting reddish brown nodule. Microscopically, the reddish brown nodule was a cholangiocarcinoma (CC) showing neuroendocrine differentiation and sarcomatoid tranformation. The yellowish tan nodule and the remaining two masses were hepatocellular carcinoma (HCC)s. On immunohistochemistry, both the adenocarcinoma and spindle sarcomatoid cells were positive for pancytokeratin, but only the adenocarcinoma cells were positive for chromogranin and carcinoembryonic antigen (CEA). Mitotic and Ki67 labeling indices as well as p53 immunopositivity were significantly increased only in the CC component. We report here on the first case of CHC in which the CC displayed neuroendocrine differentiation and sarcomatoid transformation with high mitotic and Ki67-labeling indices, as well as having p53 overexpression.
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