Journal of Pathology and Translational Medicine

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

10,166 View
336 Download
22 Web of Science
20 Crossref

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

Citations to this article as recorded by

Association between tumor morphology and efficacy of atezolizumab plus bevacizumab for advanced hepatocellular carcinoma
Nobuaki Ishihara, Shohei Komatsu, Keitaro Sofue, Eisuke Ueshima, Yoshihiko Yano, Yoshimi Fujishima, Jun Ishida, Masahiro Kido, Hidetoshi Gon, Kenji Fukushima, Takeshi Urade, Hiroaki Yanagimoto, Hirochika Toyama, Yoshihide Ueda, Yuzo Kodama, Takamichi Mura
Hepatology Research.2024;[Epub] CrossRef
Macroscopic Characterization of Hepatocellular Carcinoma: An Underexploited Source of Prognostic Factors
Stéphanie Gonvers, Sebastiao Martins-Filho, André Hirayama, Julien Calderaro, Rebecca Phillips, Emilie Uldry, Nicolas Demartines, Emmanuel Melloul, Young Nyun Park, Valérie Paradis, Swan Thung, Venancio Alves, Christine Sempoux, Ismail Labgaa
Journal of Hepatocellular Carcinoma.2024; Volume 11: 707. CrossRef
Recurrence of hepatocellular carcinoma in noncirrhotic patients with nonalcoholic fatty liver disease versus hepatitis B infection
Jungnam Lee, Jong-In Chang, Young-Joo Jin, Jeong-Hoon Lee, Ju Yeon Kim, Dong Hyun Sinn, Soon Sun Kim, Hyun Woong Lee, Sun Hong Yoo, Jung Hwan Yu, Jin-Woo Lee
European Journal of Gastroenterology & Hepatology.2023; 35(4): 431. CrossRef
Comprehensive investigating of MMR gene in hepatocellular carcinoma with chronic hepatitis B virus infection in Han Chinese population
Ning Ma, Ao Jin, Yitong Sun, Yiyao Jin, Yucheng Sun, Qian Xiao, XuanYi Sha, Fengxue Yu, Lei Yang, Wenxuan Liu, Xia Gao, Xiaolin Zhang, Lu Li
Frontiers in Oncology.2023;[Epub] CrossRef
LI-RADS Morphological Type Predicts Prognosis of Patients with Hepatocellular Carcinoma After Radical Resection
Chunhui Zhang, Rui Yang, Xinxin Wang, Yuqing Tao, Shuli Tang, Zhennan Tian, Yang Zhou
Annals of Surgical Oncology.2023; 30(8): 4876. CrossRef
From clinical variables to multiomics analysis: a margin morphology-based gross classification system for hepatocellular carcinoma stratification
Zhongqi Fan, Meishan Jin, Lei Zhang, Nanya Wang, Mingyue Li, Chuanlei Wang, Feng Wei, Ping Zhang, Xiaohong Du, Xiaodong Sun, Wei Qiu, Meng Wang, Hongbin Wang, Xiaoju Shi, Junfeng Ye, Chao Jiang, Jianpeng Zhou, Wengang Chai, Jun Qi, Ting Li, Ruoyan Zhang,
Gut.2023; 72(11): 2149. CrossRef
A clinical and pathological update on hepatocellular carcinoma
Salvatore Lorenzo Renne, Luca Di Tommaso
Journal of Liver Cancer.2022; 22(1): 14. CrossRef
An approach to grossing of hepatectomy specimens
Archana Rastogi
Indian Journal of Pathology and Microbiology.2021; 64(5): 121. CrossRef
Hepatocellular carcinoma: a clinical and pathological overview
Salvatore Lorenzo Renne, Samantha Sarcognato, Diana Sacchi, Maria Guido, Massimo Roncalli, Luigi Terracciano, Luca Di Tommaso
Pathologica.2021; 113(3): 203. CrossRef
The Clinicopathological Significance of YAP/TAZ Expression in Hepatocellular Carcinoma with Relation to Hypoxia and Stemness
Hyunjin Park, Yangkyu Lee, Kiryang Lee, Hyejung Lee, Jeong Eun Yoo, Soomin Ahn, Young Nyun Park, Haeryoung Kim
Pathology and Oncology Research.2021;[Epub] CrossRef
Adjuvant versus Neoadjuvant Immunotherapy for Hepatocellular Carcinoma: Clinical and Immunologic Perspectives
Yung-Yeh Su, Chia-Chen Li, Yih-Jyh Lin, Chiun Hsu
Seminars in Liver Disease.2021; 41(03): 263. CrossRef
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
Journal of Pathology and Translational Medicine.2021; 55(5): 338. CrossRef
Survival according to recurrence patterns after resection for transplantable hepatocellular carcinoma in HBV endemic area: Appraisal of liver transplantation strategy
Chung Gyo Seo, Sun Young Yim, Soon Ho Um, Yoo Ra Lee, Yoo Jin Lee, Tae Hyung Kim, Hyun Gil Goh, Young Sun Lee, Sang Jun Suh, Na Yeon Han, Hyuk Soon Choi, Eun Sun Kim, Bora Keum, Yeon Seok Seo, Hyung Joon Yim, Ji Hoon Kim, Dong Sik Kim, Yoon Tae Jeen, Hoon
Clinics and Research in Hepatology and Gastroenterology.2020; 44(4): 532. CrossRef
A radiomics-based biomarker for cytokeratin 19 status of hepatocellular carcinoma with gadoxetic acid–enhanced MRI
Wentao Wang, Dongsheng Gu, Jingwei Wei, Ying Ding, Li Yang, Kai Zhu, Rongkui Luo, Sheng-Xiang Rao, Jie Tian, Mengsu Zeng
European Radiology.2020; 30(5): 3004. CrossRef
Paeonol Inhibits Cell Proliferation, Migration and Invasion and Induces Apoptosis in Hepatocellular Carcinoma by Regulating miR-21-5p/KLF6 Axis

Miaoguo Cai, Wei Shao, Huijun Yu, Ye Hong, Lili Shi
Cancer Management and Research.2020; Volume 12: 5931. CrossRef
Update on Hepatocellular Carcinoma: a Brief Review from Pathologist Standpoint
Nese Karadag Soylu
Journal of Gastrointestinal Cancer.2020; 51(4): 1176. CrossRef
Clinico-Radio-Pathological and Molecular Features of Hepatocellular Carcinomas with Keratin 19 Expression
Hyungjin Rhee, Haeryoung Kim, Young Nyun Park
Liver Cancer.2020; 9(6): 663. CrossRef
Histopathological characteristics of needle core biopsy and surgical specimens from patients with solitary hepatocellular carcinoma or intrahepatic cholangiocarcinoma
Ju-Shan Wu, Ji-Liang Feng, Rui-Dong Zhu, San-Guang Liu, Da-Wei Zhao, Ning Li
World Journal of Gastrointestinal Oncology.2019; 11(5): 404. CrossRef
The strengths and weaknesses of gross and histopathological evaluation in hepatocellular carcinoma: a brief review
Sebastião N. Martins-Filho, Venâncio Avancini Ferreira Alves
Surgical and Experimental Pathology.2019;[Epub] CrossRef
Changing role of histopathology in the diagnosis and management of hepatocellular carcinoma
Archana Rastogi
World Journal of Gastroenterology.2018; 24(35): 4000. CrossRef

SALL4 Expression in Hepatocellular Carcinomas Is Associated with EpCAM-Positivity and a Poor Prognosis: Hyunjin Park, Hyejung Lee, An Na Seo, Jai Young Cho, Young Rok Choi, Yoo-Seok Yoon, Ho-Seong Han, Young Nyun Park, Haeryoung Kim; J Pathol Transl Med. 2015;49(5):373-381. Published online August 10, 2015; DOI: https://doi.org/10.4132/jptm.2015.07.09

9,798 View
76 Download
21 Web of Science
20 Crossref

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.

Citations

Citations to this article as recorded by

Stemness markers in hepatocellular carcinoma of Eastern vs. Western population: Etiology matters?
Caecilia HC Sukowati, Korri El-Khobar, Chyntia Olivia Maurine Jasirwan, Juferdy Kurniawan, Rino Alvani Gani
Annals of Hepatology.2024; 29(1): 101153. CrossRef
Research progress and prospects of AFP-positive gastric cancer
Long Zhao, Changjiang Yang, Yilin Lin, Shan Wang, Yingjiang Ye, Zhanlong Shen
Foregut Surgery.2022; 2(1): 29. CrossRef
SALL4 and microRNA: The Role of Let-7
Jun Liu, Madeline A. Sauer, Shaza G. Hussein, Junyu Yang, Daniel G. Tenen, Li Chai
Genes.2021; 12(9): 1301. CrossRef
Hepatoid Teratoma, Hepatoid Yolk Sac Tumor, and Hepatocellular Carcinoma
Khaleel I. Al-Obaidy, Sean R. Williamson, Nathan Shelman, Muhammad T. Idrees, Thomas M. Ulbright
American Journal of Surgical Pathology.2021; 45(1): 127. CrossRef
Targeting an Inducible SALL4-Mediated Cancer Vulnerability with Sequential Therapy
Junyu Yang, Chong Gao, Miao Liu, Yao-Chung Liu, Junsu Kwon, Jun Qi, Xi Tian, Alicia Stein, Yanjing V. Liu, Nikki R. Kong, Yue Wu, Shenyi Yin, Jianzhong Xi, Zhiyuan Chen, Kalpana Kumari, Hannan Wong, Hongbo Luo, Leslie E. Silberstein, Julie A.I. Thoms, Ash
Cancer Research.2021; 81(23): 6018. CrossRef
Lipoprotein‐Like Nanoparticle Carrying Small Interfering RNA Against Spalt‐Like Transcription Factor 4 Effectively Targets Hepatocellular Carcinoma Cells and Decreases Tumor Burden
William Cruz, Huang Huang, Brian Barber, Elisa Pasini, Lili Ding, Gang Zheng, Juan Chen, Mamatha Bhat
Hepatology Communications.2020; 4(5): 769. CrossRef
Hepatoid adenocarcinoma of the stomach: a unique subgroup with distinct clinicopathological and molecular features
Yakun Wang, Li Sun, Zhongwu Li, Jing Gao, Sai Ge, Cheng Zhang, Jiajia Yuan, Xicheng Wang, Jian Li, Zhihao Lu, Jifang Gong, Ming Lu, Jun Zhou, Zhi Peng, Lin Shen, Xiaotian Zhang
Gastric Cancer.2019; 22(6): 1183. CrossRef
Gynecologic Serous Carcinoma: An Immunohistochemical Analysis of Malignant Body Fluid Specimens
Shuyue Ren, William Klump
Archives of Pathology & Laboratory Medicine.2019; 143(6): 677. CrossRef
The pluripotency network in colorectal cancer pathogenesis and prognosis: an update
Ioannis A Voutsadakis
Biomarkers in Medicine.2018; 12(6): 653. CrossRef
Cancer stem cells in hepatocellular carcinoma: an overview and promising therapeutic strategies
Nuozhou Wang, Shanshan Wang, Ming-Yue Li, Bao-guang Hu, Li-ping Liu, Sheng-li Yang, Shucai Yang, Zhongqin Gong, Paul B. S. Lai, George G. Chen
Therapeutic Advances in Medical Oncology.2018; 10: 175883591881628. CrossRef
DNA demethylation induces SALL4 gene re-expression in subgroups of hepatocellular carcinoma associated with Hepatitis B or C virus infection
H Fan, Z Cui, H Zhang, S K Mani, A Diab, L Lefrancois, N Fares, P Merle, O Andrisani
Oncogene.2017; 36(17): 2435. CrossRef
Higher expression of SALL4 predicts poor cancer prognosis: A meta-analysis
Hongyu Shen, Liangpeng Li, Dandan Wang, Sujin Yang, Xiu Chen, Siying Zhou, Shanliang Zhong, Jianhua Zhao, Jinhai Tang
Cancer Biomarkers.2017; 19(4): 365. CrossRef
SALL4 suppresses PTEN expression to promote glioma cell proliferation via PI3K/AKT signaling pathway
Chuanjin Liu, Haibin Wu, Yanyan Li, Liang Shen, Renchun Yu, Hongwei Yin, Ting Sun, Chunming Sun, Youxin Zhou, Ziwei Du
Journal of Neuro-Oncology.2017; 135(2): 263. CrossRef
Liver Cancer: Molecular Characterization, Clonal Evolution and Cancer Stem Cells
Germana Castelli, Elvira Pelosi, Ugo Testa
Cancers.2017; 9(9): 127. CrossRef
Oncofetal gene SALL4 and prognosis in cancer: A systematic review with meta-analysis
Lorenzo Nicolè, Tiziana Sanavia, Nicola Veronese, Rocco Cappellesso, Claudio Luchini, Paolo Dabrilli, Ambrogio Fassina
Oncotarget.2017; 8(14): 22968. CrossRef
SALL4, the missing link between stem cells, development and cancer
Hiro Tatetsu, Nikki R. Kong, Gao Chong, Giovanni Amabile, Daniel G. Tenen, Li Chai
Gene.2016; 584(2): 111. CrossRef
A New Cell Block Method for Multiple Immunohistochemical Analysis of Circulating Tumor Cells in Patients with Liver Cancer
Soo Jeong Nam, Hyun Yang Yeo, Hee Jin Chang, Bo Hyun Kim, Eun Kyung Hong, Joong-Won Park
Cancer Research and Treatment.2016; 48(4): 1229. CrossRef
Functional and clinical significance of SALL4 in breast cancer
Ebubekir Dirican, Mustafa Akkiprik
Tumor Biology.2016; 37(9): 11701. CrossRef
MicroRNA-33b suppresses the proliferation and metastasis of hepatocellular carcinoma cells through the inhibition of Sal-like protein 4 expression
Qinggang Tian, Yao Xiao, Yanting Wu, Yun Liu, Zhiqing Song, Wenfeng Gao, Jing Zhang, Jingling Yang, Yuguo Zhang, Tuankui Guo, Furong Dai, Zhigang Sun
International Journal of Molecular Medicine.2016; 38(5): 1587. CrossRef
Oncogenic protein SALL4 and ZNF217 as prognostic indicators in solid cancers: a meta-analysis of individual studies
Ji Cheng, Jinbo Gao, Xiaoming Shuai, Kaixiong Tao
Oncotarget.2016; 7(17): 24314. CrossRef

Chemotherapy-Associated Hepatopathy in Korean Colorectal Cancer Liver Metastasis Patients: Oxaliplatin-Based Chemotherapy and Sinusoidal Injury: Soo Jeong Nam, Jai Young Cho, Hye Seung Lee, Gheeyoung Choe, Ja June Jang, Yoo-Seok Yoon, Ho-Seong Han, Haeryoung Kim; Korean J Pathol. 2012;46(1):22-29. Published online February 23, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.22

7,265 View
61 Download
12 Crossref

Abstract PDF

Background

Although chemotherapy-related hepatic injury has been reported in colorectal cancer liver metastasis (CRLM) patients, the morphologic changes caused by chemotherapeutic agents and the effect of chemotherapy on postoperative outcome remain ill-defined. A comprehensive review of the morphologic changes in the post-chemotherapy non-neoplastic liver was performed and the clinical effect of preoperative chemotherapy in CRLM patients was analyzed.

Methods

Hematoxylin-eosin, Masson's trichrome and reticulin-stained slides from non-neoplastic livers obtained from 89 CRLM patients were analyzed, and the clinicopathologic features were correlated with the status of chemotherapy exposure.

Results

Histopathologic features of sinusoidal injury (sinusoidal dilatation, centrilobular perivenular fibrosis, parenchymal extinction lesions, small vessel obliteration, and hepatocyte plate disruption) were significantly more frequent in oxaliplatin-exposed livers (p<0.05). The extent of sinusoidal dilatation was positively correlated with increasing numbers of chemotherapy cycles (p=0.022). Abnormal preoperative liver function tests were more frequently seen (p<0.05) and postoperative total bilirubin was higher in the chemotherapy group (p=0.008). Postoperative morbidity was more common in the chemotherapy group (p=0.044).

Conclusions

Sinusoidal injury is frequently seen in oxaliplatin-treated livers, and its presence, especially when extensive, should be documented in surgical pathology practice. The recognition of sinusoidal injury may provide helpful guidelines for surgeons in deciding the extent of hepatic resection.

Citations

Citations to this article as recorded by

Model establishment and microarray analysis of mice with oxaliplatin‑induced hepatic sinusoidal obstruction syndrome
Chen Zhu, Xinwei Cheng, Ping Gao, Qianyan Gao, Ximin Wang, Dong Liu, Xiuhua Ren, Chengliang Zhang
Molecular Medicine Reports.2022;[Epub] CrossRef
Oxaliplatin-induced hepatic sinusoidal obstruction syndrome
Chen Zhu, Xiuhua Ren, Dong Liu, Chengliang Zhang
Toxicology.2021; 460: 152882. CrossRef
Hepatic steatosis in patients undergoing resection of colorectal liver metastases: A target for prehabilitation? A narrative review
D.T. Doherty, P.O. Coe, L. Rimmer, S. Lapsia, A. Krige, D.A. Subar
Surgical Oncology.2019; 30: 147. CrossRef
Protective effect of Korean red ginseng on oxaliplatin-mediated splenomegaly in colon cancer
Jeonghyun Kang, Joon Seong Park, Sung Gwe Ahn, Jin Hong Lim, Seung Hyuk Baik, Dong Sup Yoon, Kang Young Lee, Joon Jeong
Annals of Surgical Treatment and Research.2018; 95(3): 161. CrossRef
Use of Imaging to Predict Complete Response of Colorectal Liver Metastases after Chemotherapy: MR Imaging versus CT Imaging
Min Jung Park, Nurhee Hong, Kyunghwa Han, Min Ju Kim, Yoon Jin Lee, Yang Shin Park, Sung Eun Rha, Sumi Park, Won Jae Lee, Seong Ho Park, Chang Hee Lee, Chung Mo Nam, Chansik An, Hye Jin Kim, Honsoul Kim, Mi-Suk Park
Radiology.2017; 284(2): 423. CrossRef
Systematic review of the influence of chemotherapy-associated liver injury on outcome after partial hepatectomy for colorectal liver metastases
J Zhao, K M C van Mierlo, J Gómez-Ramírez, H Kim, C H C Pilgrim, P Pessaux, S S Rensen, E P van der Stok, F G Schaap, O Soubrane, T Takamoto, L Viganò, B Winkens, C H C Dejong, S W M Olde Damink, I García Sanz, E Martín Pérez, J Y Cho, Y R Choi, W Phillip
British Journal of Surgery.2017; 104(8): 990. CrossRef
Hepatic Lesions that Mimic Metastasis on Radiological Imaging during Chemotherapy for Gastrointestinal Malignancy: Recent Updates
Sung-Hye You, Beom Jin Park, Yeul Hong Kim
Korean Journal of Radiology.2017; 18(3): 413. CrossRef
Changes in Noninvasive Liver Fibrosis Indices and Spleen Size During Chemotherapy
Sehhoon Park, Hwi Young Kim, Haeryoung Kim, Jin Hyun Park, Jung Ho Kim, Ki Hwan Kim, Won Kim, In Sil Choi, Yong Jin Jung, Jin-Soo Kim
Medicine.2016; 95(2): e2454. CrossRef
Hepar lobatum carcinomatosum associated with liver metastases from breast cancer: Report of five cases
N. Alberti, D. Bechade, F. Dupuis, A. Crombe, A. Neuville, M. Debled, J. Palussiere, X. Buy, J.-T. Perez, M. Desjardin, N. Frulio, M. Kind
Diagnostic and Interventional Imaging.2015; 96(1): 73. CrossRef
Sinusoidal obstruction syndrome after oxaliplatin-based chemotherapy
An Na Seo, Haeryoung Kim
Clinical and Molecular Hepatology.2014; 20(1): 81. CrossRef
Chemotherapy-induced Focal Hepatopathy in Patients with Gastrointestinal Malignancy: Gadoxetic Acid–enhanced and Diffusion-weighted MR Imaging with Clinical-Pathologic Correlation
Na Yeon Han, Beom Jin Park, Deuk Jae Sung, Min Ju Kim, Sung Bum Cho, Chang Hee Lee, Yun-Jin Jang, So Yeon Kim, Dong Sik Kim, Soon Ho Um, Nam Hee Won, Kyung Sook Yang
Radiology.2014; 271(2): 416. CrossRef
Histopathologic Manifestations of Drug-induced Hepatotoxicity
Xuchen Zhang, Jie Ouyang, Swan N. Thung
Clinics in Liver Disease.2013; 17(4): 547. CrossRef

First
Prev
Page of 1
Next
Last

Search