Journal of Pathology and Translational Medicine

Original Article

Identification of invasive subpopulations using spatial transcriptome analysis in thyroid follicular tumors: Ayana Suzuki, Satoshi Nojima, Shinichiro Tahara, Daisuke Motooka, Masaharu Kohara, Daisuke Okuzaki, Mitsuyoshi Hirokawa, Eiichi Morii; J Pathol Transl Med. 2024;58(1):22-28. Published online January 10, 2024; DOI: https://doi.org/10.4132/jptm.2023.11.21

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Abstract PDF: Background
Follicular tumors include follicular thyroid adenomas and carcinomas; however, it is difficult to distinguish between the two when the cytology or biopsy material is obtained from a portion of the tumor. The presence or absence of invasion in the resected material is used to differentiate between adenomas and carcinomas, which often results in the unnecessary removal of the adenomas. If nodules that may be follicular thyroid carcinomas are identified preoperatively, active surveillance of other nodules as adenomas is possible, which reduces the risk of surgical complications and the expenses incurred during medical treatment. Therefore, we aimed to identify biomarkers in the invasive subpopulation of follicular tumor cells.
Methods
We performed a spatial transcriptome analysis of a case of follicular thyroid carcinoma and examined the dynamics of CD74 expression in 36 cases.
Results
We identified a subpopulation in a region close to the invasive area, and this subpopulation expressed high levels of CD74. Immunohistochemically, CD74 was highly expressed in the invasive and peripheral areas of the tumor.
Conclusions
Although high CD74 expression has been reported in papillary and anaplastic thyroid carcinomas, it has not been analyzed in follicular thyroid carcinomas. Furthermore, the heterogeneity of CD74 expression in thyroid tumors has not yet been reported. The CD74-positive subpopulation identified in this study may be useful in predicting invasion of follicular thyroid carcinomas.

Case Study

Primary testicular carcinoid tumor with marked lymphovascular invasion: Hyun Jung Lee, Joon Young Park, So Young Kim, Chung Su Hwang, Jung Hee Lee, Dong Hoon Shin, Jee Yeon Kim; J Pathol Transl Med. 2021;55(6):410-414. Published online October 20, 2021; DOI: https://doi.org/10.4132/jptm.2021.09.11

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Testicular carcinoid tumors are very rare, accounting for less than 1% of all testicular tumors. We report a rare case of a testicular carcinoid tumor with extensive lymphatic invasion. A 42-year-old man presented with a painless, enlarged right testicular mass. There was no history of injury or discomfort in this region. Right radical orchiectomy was performed, which showed a well-defined, non-encapsulated solid white mass with calcification (7.0 × 4.5 × 3.5 cm) and absence of cystic components. Microscopic examination using hematoxylin and eosin staining of the tumor sections identified organoid, trabecular, and solid patterns with rosette formation. Extensive multifocal lymphatic invasion was observed. Immunohistochemistry was positive for synaptophysin, chromogranin, and CD56. Testicular carcinoid tumors usually show good prognoses; however, there was extensive lymphovascular invasion in this case. Thus, in the case of unusual presentation of the disease, close follow-up is necessary.

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Testicular Primary Well-Differentiated Neuroendocrine Tumor: Clinicopathologic, Immunohistochemical, and Molecular Characterization of Two Patients
Liwei Jia, Bo Zhang, Daniel Shen, Prasad R. Koduru
International Journal of Surgical Pathology.2024;[Epub] CrossRef

Original Articles

Double cocktail immunostains with high molecular weight cytokeratin and GATA-3: useful stain to discriminate in situ involvement of prostatic ducts or acini from stromal invasion by urothelial carcinoma in the prostate: Junghye Lee, Youngeun Yoo, Sanghui Park, Min-Sun Cho, Sun Hee Sung, Jae Y. Ro; J Pathol Transl Med. 2020;54(2):146-153. Published online February 10, 2020; DOI: https://doi.org/10.4132/jptm.2019.11.12

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Abstract PDF

Background
Distinguishing prostatic stromal invasion (PSI) by urothelial carcinoma (UC) from in situ UC involving prostatic ducts or acini with no stromal invasion (in situ involvement) may be challenging on hematoxylin and eosin stained sections. However, the distinction between them is important because cases with PSI show worse prognosis. This study was performed to assess the utility of double cocktail immunostains with high molecular weight cytokeratin (HMWCK) and GATA-3 to discriminate PSI by UC from in situ UC involvement of prostatic ducts or acini in the prostate.
Methods
Among 117 radical cystoprostatectomy specimens for bladder UCs, 25 cases showed secondary involvement of bladder UC in prostatic ducts/acini only or associated stromal invasion and of these 25 cases, seven cases revealed equivocal PSI. In these seven cases with equivocal PSI, HMWCK, and GATA-3 double immunohistochemical stains were performed to identify whether this cocktail stain is useful to identify the stromal invasion.
Results
In all cases, basal cells of prostate glands showed strong cytoplasmic staining for HMWCK and UC cells showed strong nuclear staining for GATA-3. In cases with stromal invasion of UC, GATA-3-positive tumor cells in the prostatic stroma without surrounding HMWCK-positive basal cells were highlighted and easily recognized. Among seven equivocal cases, two cases showed PSI and five in situ UC in the prostate. In two cases, the original diagnoses were revised.
Conclusions
Our study suggested that HMWCK and GATA-3 double stains could be utilized as an adjunct method in the distinction between PSI by UC from in situ UC involving prostatic ducts or acini.

Citations

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Aberrant expression of GATA3 in metastatic adenocarcinoma of the prostate: an important pitfall
João Lobo, Nazario P Tenace, Sofia Cañete‐Portillo, Isa Carneiro, Rui Henrique, Roberta Lucianò, Lara R Harik, Cristina Magi‐Galluzzi
Histopathology.2024; 84(3): 507. CrossRef
Utility of D2-40, Cytokeratin 5/6, and High–Molecular-weight Cytokeratin (Clone 34βE12) in Distinguishing Intraductal Spread of Urothelial Carcinoma From Prostatic Stromal Invasion
Oleksii A. Iakymenko, Laurence M. Briski, Katiana S. Delma, Merce Jorda, Oleksandr N. Kryvenko
American Journal of Surgical Pathology.2022; 46(4): 454. CrossRef

The Major Role of NF-κB in the Depth of Invasion on Acral Melanoma by Decreasing CD8⁺ T Cells: Hermin Aminah Usman, Bethy S. Hernowo, Maringan Diapari Lumban Tobing, Reti Hindritiani; J Pathol Transl Med. 2018;52(3):164-170. Published online April 20, 2018; DOI: https://doi.org/10.4132/jptm.2018.04.04

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Abstract PDF

Background
The tumor microenvironment including immune surveillance affects malignant melanoma (MM) behavior. Nuclear factor κB (NF-κB) stimulates the transcription of various genes in the nucleus and plays a role in the inflammatory process and in tumorigenesis. CD8+ T cells have cytotoxic properties important in the elimination of tumors. However, inhibitory receptors on the cell surface will bind to programmed death-ligand 1 (PD-L1), causing CD8+ T cells to lose their ability to initiate an immune response. This study analyzed the association of NF-κB and PD-L1 expression levels and CD8+ T-cell counts with depth of invasion of acral MM, which may be a predictor of aggressiveness related to an increased risk of metastasis.
Methods
A retrospective cross-sectional study was conducted in the Department of Anatomical Pathology, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin Hospital using 96 cases of acral melanoma. Immunohistochemical staining was performed on paraffin blocks using anti–NF-κB, –PD-L1, and -CD8 antibodies and invasion depth was measured using dotSlide-imaging software.
Results
The study showed significant associations between the individual expression of NF-κB and PD-L1 and CD8+ T-cell number, with MM invasion depth. NF-κB was found to be a confounding variable of CD8+ T-cell number (p < .05), but not for PD-L1 expression (p = .154). Through multivariate analysis it was found that NF-κB had the greatest association with the depth of invasion (p < .001), whereas PD-L1 was unrelated to the depth of invasion because it depends on the number of CD8+ T cells (p = .870).
Conclusions
NF-κB plays a major role in acral MM invasion, by decreasing the number of CD8+ T cells in acral MM.

Citations

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Possible Mechanisms of Oxidative Stress-Induced Skin Cellular Senescence, Inflammation, and Cancer and the Therapeutic Potential of Plant Polyphenols
Hui-Min Liu, Ming-Yan Cheng, Meng-Han Xun, Zhi-Wei Zhao, Yun Zhang, Wei Tang, Jun Cheng, Jia Ni, Wei Wang
International Journal of Molecular Sciences.2023; 24(4): 3755. CrossRef
Clinical features, molecular pathology, and immune microenvironmental characteristics of acral melanoma
Jianping Gui, Zhen Guo, Di Wu
Journal of Translational Medicine.2022;[Epub] CrossRef
High Expression of COX-2 Associated with the Depth of Invasion on Acral Melanoma by Increasing TGF-β1
Nastassa Gipsyianti, Afiati Aziz, Bethy S Hernowo, Hermin A Usman
Clinical, Cosmetic and Investigational Dermatology.2021; Volume 14: 209. CrossRef
More than just acral melanoma: the controversies of defining the disease
Sara S Bernardes, Ingrid Ferreira, David E Elder, Aretha B Nobre, Héctor Martínez‐Said, David J Adams, Carla Daniela Robles‐Espinoza, Patricia A Possik
The Journal of Pathology: Clinical Research.2021; 7(6): 531. CrossRef
CD103+ T Lymphocyte Count Linked to the Thickness of Invasion on Acral Melanoma without E-Cadherin Involvement
Fauzan Ali Zainal Abidin, Hermin Aminah Usman, Sri Suryanti, Bethy S Hernowo
Clinical, Cosmetic and Investigational Dermatology.2021; Volume 14: 1783. CrossRef
Translational pathology, genomics and the development of systemic therapies for acral melanoma
Yian Ann Chen, Jamie K. Teer, Zeynep Eroglu, Jheng-Yu Wu, John M. Koomen, Florian A. Karreth, Jane L. Messina, Keiran S.M. Smalley
Seminars in Cancer Biology.2020; 61: 149. CrossRef

Extramural Perineural Invasion in pT3 and pT4 Gastric Carcinomas: Alejandro España-Ferrufino, Leonardo S. Lino-Silva, Rosa A. Salcedo-Hernández; J Pathol Transl Med. 2018;52(2):79-84. Published online November 9, 2017; DOI: https://doi.org/10.4132/jptm.2017.11.01

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Abstract PDF

Background
Perineural invasion (PNI) is widely studied in malignant tumors, and its prognostic significance is well demonstrated. Most studies have focused on evaluating the mural PNI (mPNI); however, extramural PNI (ePNI) may influence the prognosis in gastric cancer. We evaluated the prognostic value of ePNI compared with mPNI in gastric cancer in this observational comparative cross-sectional study.
Methods
Seventy-three pT3 and pT4 gastric carcinomas with PNI were evaluated. Forty-eight (65.7%) were in the mPNI group and the remaining in the ePNI group.
Results
Clinicopathologic characteristics between the two groups were similar, except for the outcomes. The 5-year disease-specific survival (DSS) rate was 64% for the mPNI group and 50% for the ePNI group (p=.039), a difference that did not remain significant in multivariate analysis. The only independent adverse prognostic factor in multivariate analysis was the presence of lymph node metastasis (hazard ratio, 1.757; 95% confidence interval, 1.082 to 2.854; p=.023).
Conclusions
We demonstrated the prognostic effect of ePNI for DSS in surgically resected pT3–pT4 gastric cancer patients. ePNI could be considered in the staging and prognostic systems of gastric cancer to stratify patients with a high risk of recurrence.

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Meng Huang, Gu Gong, Yicheng Deng, Xinmiao Long, Wenyong Long, Qing Liu, Wei Zhao, Rufu Chen
Medicine Advances.2023; 1(3): 173. CrossRef
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Xinyu Li, Xueqiang Peng, Shuo Yang, Shibo Wei, Qing Fan, Jingang Liu, Liang Yang, Hangyu Li
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Deborah A. Silverman, Vena K. Martinez, Patrick M. Dougherty, Jeffrey N. Myers, George A. Calin, Moran Amit
Cancer Research.2021; 81(6): 1431. CrossRef
Perineural Invasion and Postoperative Adjuvant Chemotherapy Efficacy in Patients With Gastric Cancer
Qing Tao, Wen Zhu, Xiaohui Zhao, Mei Li, Yongqian Shu, Deqiang Wang, Xiaoqin Li
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Perineural invasion as a predictive factor for survival outcome in gastric cancer patients: a systematic review and meta-analysis
Bochao Zhao, Wu Lv, Di Mei, Rui Luo, Shiyang Bao, Baojun Huang, Jie Lin
Journal of Clinical Pathology.2020; 73(9): 544. CrossRef
Consensus-Expressed CXCL8 and MMP9 Identified by Meta-Analyzed Perineural Invasion Gene Signature in Gastric Cancer Microarray Data
Xiuzhi Jia, Minjia Lu, Chen Rui, Ying Xiao
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Aquaporin 1 Is an Independent Marker of Poor Prognosis in Lung Adenocarcinoma: Sumi Yun, Ping-Li Sun, Yan Jin, Hyojin Kim, Eunhyang Park, Soo Young Park, Kyuho Lee, Kyoungyul Lee, Jin-Haeng Chung; J Pathol Transl Med. 2016;50(4):251-257. Published online June 7, 2016; DOI: https://doi.org/10.4132/jptm.2016.03.30

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Abstract PDF

Background
Aquaporin 1 (AQP1) overexpression has been shown to be associated with uncontrolled cell replication, invasion, migration, and tumor metastasis. We aimed to evaluate AQP1 expression in lung adenocarcinomas and to examine its association with clinicopathological features and prognostic significance. We also investigated the association between AQP1 overexpression and epithelial-mesenchymal transition (EMT) markers.
Methods
We examined AQP1 expression in 505 cases of surgically resected lung adenocarcinomas acquired at the Seoul National University Bundang Hospital from 2003 to 2012. Expression of AQP1 and EMT-related markers, including Ecadherin and vimentin, were analyzed by immunohistochemistry and tissue microarray.
Results
AQP1 overexpression was associated with several aggressive pathological parameters, including venous invasion, lymphatic invasion, and tumor recurrence. AQP1 overexpression tended to be associated with higher histological grade, advanced pathological stage, and anaplastic lymphoma kinase (ALK) translocation; however, these differences were not statistically significant. In addition, AQP1 overexpression positively correlated with loss of E-cadherin expression and acquired expression of vimentin. Lung adenocarcinoma patients with AQP1 overexpression showed shorter progression- free survival (PFS, 46.1 months vs. 56.2 months) compared to patients without AQP1 overexpression. Multivariate analysis confirmed that AQP1 overexpression was significantly associated with shorter PFS (hazard ratio, 1.429; 95% confidence interval, 1.033 to 1.977; p=.031).
Conclusions
AQP1 overexpression was thereby concluded to be an independent factor of poor prognosis associated with shorter PFS in lung adenocarcinoma. These results suggested that AQP1 overexpression might be considered as a prognostic biomarker of lung adenocarcinoma.

Citations

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Aquaporins in Cancer Biology
Chul So Moon, David Moon, Sung Koo Kang
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A Comprehensive Prognostic Analysis of Tumor-Related Blood Group Antigens in Pan-Cancers Suggests That SEMA7A as a Novel Biomarker in Kidney Renal Clear Cell Carcinoma
Yange Wang, Chenyang Li, Xinlei Qi, Yafei Yao, Lu Zhang, Guosen Zhang, Longxiang Xie, Qiang Wang, Wan Zhu, Xiangqian Guo
International Journal of Molecular Sciences.2022; 23(15): 8799. CrossRef
Differential modulation of lung aquaporins among other pathophysiological markers in acute (Cl2 gas) and chronic (carbon nanoparticles, cigarette smoke) respiratory toxicity mouse models
Sukanta S. Bhattacharya, Brijesh Yadav, Ekta Yadav, Ariel Hus, Niket Yadav, Perminder Kaur, Lauren Rosen, Roman Jandarov, Jagjit S. Yadav
Frontiers in Physiology.2022;[Epub] CrossRef
Aquaporin water channels as regulators of cell-cell adhesion proteins
Sarannya Edamana, Frédéric H. Login, Soichiro Yamada, Tae-Hwan Kwon, Lene N. Nejsum
American Journal of Physiology-Cell Physiology.2021; 320(5): C771. CrossRef
Targeting Aquaporins in Novel Therapies for Male and Female Breast and Reproductive Cancers
Sidra Khan, Carmela Ricciardelli, Andrea J. Yool
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Targeting ion channels for the treatment of lung cancer
Liqin Zhang, Shuya Bing, Mo Dong, Xiaoqiu Lu, Yuancheng Xiong
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer.2021; 1876(2): 188629. CrossRef
Comprehensive Analysis of Aquaporin Superfamily in Lung Adenocarcinoma
Guofu Lin, Luyang Chen, Lanlan Lin, Hai Lin, Zhifeng Guo, Yingxuan Xu, Chanchan Hu, Jinglan Fu, Qinhui Lin, Wenhan Chen, Yiming Zeng, Yuan Xu
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Aquaporin 1, 3, and 5 Patterns in Salivary Gland Mucoepidermoid Carcinoma: Expression in Surgical Specimens and an In Vitro Pilot Study
Mérin Barbara Stamboni, Ágatha Nagli de Mello Gomes, Milena Monteiro de Souza, Katia Klug Oliveira, Claudia Fabiana Joca Arruda, Fernanda de Paula, Barbara Beltrame Bettim, Márcia Martins Marques, Luiz Paulo Kowalski, Clóvis Antônio Lopes Pinto, Victor El
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Combined Systematic Review and Transcriptomic Analyses of Mammalian Aquaporin Classes 1 to 10 as Biomarkers and Prognostic Indicators in Diverse Cancers
Pak Hin Chow, Joanne Bowen, Andrea J Yool
Cancers.2020; 12(7): 1911. CrossRef
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Ekta Yadav, Niket Yadav, Ariel Hus, Jagjit S. Yadav
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Dissecting gene‐environment interactions: A penalized robust approach accounting for hierarchical structures
Cen Wu, Yu Jiang, Jie Ren, Yuehua Cui, Shuangge Ma
Statistics in Medicine.2018; 37(3): 437. CrossRef
Immunohistochemical Expression of Aquaporin-1 in Fluoro-Edenite-Induced Malignant Mesothelioma: A Preliminary Report
Giuseppe Angelico, Rosario Caltabiano, Carla Loreto, Antonio Ieni, Giovanni Tuccari, Caterina Ledda, Venerando Rapisarda
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Mechanisms of Aquaporin-Facilitated Cancer Invasion and Metastasis
Michael L. De Ieso, Andrea J. Yool
Frontiers in Chemistry.2018;[Epub] CrossRef
Aquaporin 1 suppresses apoptosis and affects prognosis in esophageal squamous cell carcinoma
Yuzo Yamazato, Atsushi Shiozaki, Daisuke Ichikawa, Toshiyuki Kosuga, Katsutoshi Shoda, Tomohiro Arita, Hirotaka Konishi, Shuhei Komatsu, Takeshi Kubota, Hitoshi Fujiwara, Kazuma Okamoto, Mitsuo Kishimoto, Eiichi Konishi, Yoshinori Marunaka, Eigo Otsuji
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Aquaporin 1 expression is associated with response to adjuvant chemotherapy in stageï¿½II and III colorectal cancer
Hideko Imaizumi, Keiichiro Ishibashi, Seiichi Takenoshita, Hideyuki Ishida
Oncology Letters.2018;[Epub] CrossRef
Aquaporin 3 facilitates tumor growth in pancreatic cancer by modulating mTOR signaling
Xunwei Huang, Li Huang, Minhua Shao
Biochemical and Biophysical Research Communications.2017; 486(4): 1097. CrossRef
Prognostic implication of aquaporin 1 overexpression in resected lung adenocarcinoma†
Guido Bellezza, Jacopo Vannucci, Fortunato Bianconi, Giulio Metro, Rachele Del Sordo, Marco Andolfi, Ivana Ferri, Paola Siccu, Vienna Ludovini, Francesco Puma, Angelo Sidoni, Lucio Cagini
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Tumor Sprouting in Papillary Thyroid Carcinoma Is Correlated with Lymph Node Metastasis and Recurrence: Eunjung Lee, Wonkyung Jung, Jeong-Soo Woo, Jae Bok Lee, Bong Kyung Shin, Han Kyeom Kim, Aeree Kim, Baek-hui Kim; Korean J Pathol. 2014;48(2):117-125. Published online April 28, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.2.117

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Abstract PDF

Background

Identification of poor prognostic factors in papillary thyroid carcinoma (PTC) patients is important for the patients' care and follow-up. We can sometimes see small tumor clusters without desmoplasia and no evidence of lymphatic emboli around the main tumor mass of PTC. We termed this form of tumor clustering, 'tumor sprouting,' and determined whether these tumors correlate with lymphovascular invasion, lymph node metastasis, and recurrence.

Methods

We analyzed a total of 204 cases of papillary thyroid macrocarcinoma. Number, size and distance from the main tumor of the tumor sprouting were observed and analyzed with clinicopathologic characteristics.

Results

Tumor sprouting was observed in 101 patients. Presence of tumor sprouting was significantly associated with positive resection margin (p=.002), lymphovascular invasion (p=.001), lymph node metastasis (p<.001), and recurrence (p=.004). Univariate analysis of recurrence-free survival revealed that tumor multiplicity (p=.037), positive resection margin (p=.007), lymphovascular invasion (p=.004), lymph node metastasis (p<.001), and tumor sprouting (p=.004) were poor prognostic factors. In multivariate analysis, positive resection margin was an independent poor prognostic factor of recurrence.

Conclusions

In conclusion, tumor sprouting is significantly correlated with lymph node metastasis and recurrence. Evaluation of tumor sprouting in PTC patients could be helpful in predicting tumor recurrence or lymph node metastasis.

Citations

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Significance of Lymphovascular Invasion as a Prognostic Factor in Patients with Papillary Thyroid Cancer: a Systematic Review and Meta-Analysis
Ho-Ryun Won, Bon Seok Koo
International Journal of Thyroidology.2023; 16(2): 157. CrossRef
Peripheral Versus Intraparenchymal Papillary Thyroid Microcarcinoma: Different Morphologies and PD-L1 Expression
Bozidar Kovacevic, Dragana Vucevic, Snezana Cerovic, Catarina Eloy
Head and Neck Pathology.2022; 16(1): 200. CrossRef
Lymphovascular invasion and risk of recurrence in papillary thyroid carcinoma
Katy Wagner, Earl Abraham, Bryan Tran, David Roshan, James Wykes, Peter Campbell, Ardalan Ebrahimi
ANZ Journal of Surgery.2020; 90(9): 1727. CrossRef
The Predictors of Multicentricity in Well-Differentiated Thyroid Cancer
Mohamed Hegazi, Waleed El Nahas, Mohamed Elmetwally, Amr Hassan, Waleed Gado , Islam Abdou, Ahmed Senbel, Mohamed Samir Abou-Sheishaa
Journal of Analytical Oncology.2018; 7(4): 65. CrossRef
Prognostic impact of vascular invasion in differentiated thyroid carcinoma: a systematic review and meta-analysis
Huy Gia Vuong, Tetsuo Kondo, Uyen N P Duong, Thong Quang Pham, Naoki Oishi, Kunio Mochizuki, Tadao Nakazawa, Lewis Hassell, Ryohei Katoh
European Journal of Endocrinology.2017; 177(2): 207. CrossRef
Detection of Tumor Multifocality Is Important for Prediction of Tumor Recurrence in Papillary Thyroid Microcarcinoma: A Retrospective Study and Meta-Analysis
Jung-Soo Pyo, Jin Hee Sohn, Guhyun Kang
Journal of Pathology and Translational Medicine.2016; 50(4): 278. CrossRef

ERG Immunohistochemistry as an Endothelial Marker for Assessing Lymphovascular Invasion: Sehun Kim, Hyung Kyu Park, Ho Young Jung, So-Young Lee, Kyueng-Whan Min, Wook Youn Kim, Hye Seung Han, Wan Seop Kim, Tae Sook Hwang, So Dug Lim; Korean J Pathol. 2013;47(4):355-364. Published online August 26, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.4.355

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Abstract PDF

Background

ERG, a member of the ETS family of transcription factors, is a highly specific endothelial marker. We investigated whether the use of ERG immunostaining can help pathologists detect lymphovascular invasion (LVI) and decrease interobserver variability in LVI diagnosis.

Methods

Fifteen cases of surgically resected colorectal cancers with hepatic metastasis were selected and the most representative sections for LVI detection were immunostained with ERG, CD31, and D2-40. Eight pathologists independently evaluated LVI status on hematoxylin and eosin (H&E) and the corresponding immunostained sections and then convened for a consensus meeting. The results were analyzed by kappa (κ) statistics.

Results

The average rate of LVI positivity was observed in 43% with H&E only, 10% with CD31, 29% with D2-40, and 16% with ERG. Agreement among pathologists was fair for H&E only (κ=0.27), D2-40 (κ=0.21), ERG (κ=0.23), and was moderate for CD31 (κ=0.55). Consensus revealed that ERG nuclear immunoreactivity showed better visual contrast of LVI detection than the other staining, with improved agreement and LVI detection rate (κ=0.65, LVI positivity rate 80%).

Conclusions

The present study demonstrated a superiority with ERG immunostaining and indicated that ERG is a promising panendothelial marker that might help pathologists increase LVI detection and decrease interobserver variability in LVI diagnosis.

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Review & Perspective

The New 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society Classification of Lung Adenocarcinoma in Resected Specimens: Clinicopathologic Relevance and Emerging Issues: Seung Yeon Ha, Mee Sook Roh; Korean J Pathol. 2013;47(4):316-325. Published online August 26, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.4.316

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Abstract PDF

Pathologists play an increasingly important role in personalized medicine for patients with lung cancer as a result of the newly recognized relationship between histologic classification and molecular change. In 2011, the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) proposed a new architectural classification for invasive lung adenocarcinomas to provide uniform terminology and diagnostic criteria. This review highlighted the evolution of the classification of lung adenocarcinomas in resected specimens with special respect to both histologic subtyping and invasion. Histologic subtyping of lung adenocarcinoma has been updated based on five major predominant patterns. New concepts of adenocarcinoma in situ and minimally invasive adenocarcinomas have been introduced to define the condition of patients who are expected to have excellent survival. Although the new IASLC/ATS/ERS classification has promising clinical relevance, significant clarification remains necessary for the definitions of subtyping and invasion. More precise definitions and subsequent better education on the interpretation of terminology will be helpful for future studies.

Citations

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Tumor heterogeneity assessed by texture analysis on contrast-enhanced CT in lung adenocarcinoma: association with pathologic grade
Ying Liu, Shichang Liu, Fangyuan Qu, Qian Li, Runfen Cheng, Zhaoxiang Ye
Oncotarget.2017; 8(32): 53664. CrossRef
Clinicopathological and prognostic significance of metastasis-associated protein 1 expression and its correlation with angiogenesis in lung invasive adenocarcinomas, based on the 2011 IASLC/ATS/ERS classification
SHUHAI LI, HUI TIAN, WEIMING YUE, LIN LI, CUN GAO, LIBO SI, WENSI HU, LEI QI, MING LU, CHUANLE CHENG, JINGJING CUI, GUANQING CHEN
Oncology Letters.2016; 11(1): 224. CrossRef
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Original Articles

Proposal for Creating a Guideline for Cancer Registration of Microinvasive Tumors of the Breast and Ovary (II): Jin Hee Sohn, Gyungyub Gong, Kyu Rae Kim, Chang Suk Kang, Youn Soo Lee, Jin Man Kim, Woo Hee Jung, Kwang Sun Suh; Korean J Pathol. 2012;46(3):226-232. Published online June 22, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.226

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Abstract PDF

Background

Cancer registration in Korea has a longer than 30-years of history, during which time cancer registration has improved and become well-organized. Cancer registries are fundamental for cancer control and multi-center collaborative research. However, there have been discrepancies in assigning behavior codes. Thus, we intend to propose appropriate behavior codes for the International Classification of Disease Oncology, 3rd edition (ICD-O-3) for microinvasive tumors of the ovary and breast not only to improve the quality of the cancer registry but also to prevent conflicts.

Methods

As in series I, two pathology study groups and the Cancer Registration Committee of the Korean Society of Pathologists (KSP) participated. To prepare a questionnaire on provisional behavior code, the relevant subjects were discussed in the workshop, and consensus was obtained by convergence of opinion from members of KSP.

Results

Microinvasive tumor of the breast should be designated as a microinvasive carcinoma which was proposed as malignant tumor (/3). Serous borderline tumor with microinvasion of the ovary was proposed as borderline tumor (/1), and mucinous borderline tumor with microinvasion of the ovary as either borderline (/1) or carcinoma (/3) according to the tumor cell nature.

Conclusions

Some issues should be elucidated with the accumulation of more experience and knowledge. Here, however, we present our second proposal.

Citations

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Update on the Proposal for Creating a Guideline for Cancer Registration of the Gastrointestinal Tumors (I-2)
Eun Sun Jung, Yun Kyung Kang, Mee-Yon Cho, Joon Mee Kim, Won Ae Lee, Hee Eun Lee, Sunhoo Park, Jin Hee Sohn, So-Young Jin
Korean Journal of Pathology.2012; 46(5): 443. CrossRef
A Proposal for Creating a Guideline for Cancer Registration of the Fibromatosis, PEComa Group, Malignant LymphomaIn Situand Dendritic Cell Tumors (III)
Changyoung Yoo, Chang Suk Kang, Yoon La Choi, Hye Yoon Kang, Jin Man Kim, Young Hye Koh, Joo Hee Lee, Seung Sook Lee, In Sun Kim, Dong Hoon Kim, Yong Ku Park, Jin Hee Sohn
Korean Journal of Pathology.2012; 46(5): 436. CrossRef

Expression of E-cadherin and p53 Proteins in Gastric Adenocarcinoma.: Sook Hee Hong, Mee Sook Roh; Korean J Pathol. 1999;33(2):80-87.

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Abstract: The gastric carcinoma shows various molecular and genetic alterations in its development and progression. There are evidences that the changes of the expression of cell adhesion molecules affect the morphogenesis of the tumor as well as the tumor progression and metastasis. The purpose of this study is the evaluation of the expression pattern of a cell adhesion molecule, E-cadherin, and a tumor suppression gene, p53, by immunohistochemical stain and the relationship of their expressions with clinicopathologic findings in gastric adenocarcinoma tissue. The E-cadherin expression was absent or reduced in 93 cases (73.2%) and p53 was positive in 98 cases (77.2%) of 127 gastric adenocarcinomas. The frequency of reduced E-cadherin expression was significantly higher in poorly differentiated adenocarcinomas (p=0.04) and in diffuse type (p=0.01), but that of p53 positivity was not significantly correlated with tumor differentiation. Both proteins showed no correlation with depth of invasion, lymph node and distant metastasis, and tumor stage. There was no correlation between E-cadherin and p53 expression. This study indicates that the altered expressions of E-cadherin and p53 are associated with the development of intestinal and diffuse types of gastric adenocarcinoma and the differentiation of the gastric adenocarcinoma is affected by cell adhesion mediated by E-cadherin, but the modes of tumor progression and metastasis are not affected by E-cadherin and p53.

Expression of p53 and Matrix Metalloproteinase-2 Proteins in Colorectal Adenocarcinoma.: Seong Jin Cho, Hwa Eun Oh, Yang Seok Chae; Korean J Pathol. 2000;34(7):494-500.

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Abstract PDF: The p53 gene is believed to play an important role through the mutation and overexpression in the progression of various human malignant tumors. The type IV collagenase (matrix metalloproteinase: MMP-2) initiates the degradation of the extracellular matrix, and consequently may play a role in the tumor invasion and metastasis. To investigate the correlation between clinicopathologic features of the colorectal adenocarcinomas and benign tumors and expression of p53 and MMP-2 proteins, we performed an immunohistochemical study on 40 colorectal adenocarcinomas, 20 adenomas and 20 hyperplastic polyps by using the antibodies to p53 and MMP-2 proteins. The positive expression rate of the p53 protein in adenocarcinomas was 62.5% and significantly higher than in benign tumors. The positive expression rate of the MMP-2 protein was 47.5% in adenocarcinomas, but there was no expression of MMP-2 protein in benign tumors. The difference in p53 and MMP-2 expression rates between malignant and non-malignant tumors was statistically significant. The positive expression rate of p53 protein in the non-metastatic and metastatic adenocarcinomas was 59.1 and 66.7%, respectively. The positive expression rate of MMP-2 protein in the non-metastatic and metastatic adencarcinomas was 45.5 and 50.0%, respectively. The correlation between several clinicopathologic features and expression of p53 and MMP-2 protein was not statistically significant, but the rate of positive MMP-2 immunoreactivity showed a statistically significant difference between Astler-Coller stage B1 C1 group and B2 C2 group of adenocarcinoma (p=0.0431). We concluded that the expression of p53 and MMP-2 protein contributes to the cancer development and MMP-2 may play a certain role in the invasiveness of the colorectal tumor. p53 and MMP-2 protein expression is not correlated with lymph node metastasis.

Expression of p53 Protein and Ki-67 in Atypical Ductal Hyperplasia, Ductal Carcinoma in Situ, and Microinvasive Ductal Carcinoma of the Breast.: Yi Kyeong Chun, Hye Sun Kim, Yee Jeong Kim, Sung Ran Hong, Hy Sook Kim, Byung Jun Park, Sung Su Kang, Ji Hyun Lee, Sung Kong Lee, Sun Hee Sung, Woon Sup Han; Korean J Pathol. 2000;34(9):665-672.

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Abstract PDF: Mutation of the p53 gene is one of the most common genetic alterations in invasive breast carcinoma. However, it is unclear that the mutation usually occurs in noninvasive breast lesions. It might be expected that there is a correlation between histologic progression of breast lesions and proliferative rate. We investigated the expression of p53 protein and Ki-67 labelling index (LI) using immunohistochemistry in 16 ductal carcinoma in situ with microinvasion (DCIS-Mi), 56 DCIS, 15 atypical ductal hyperplasia (ADH), and 7 intraductal hyperplasia (IDH). Expression of p53 protein was detected in 33.9% of DCIS and 56.3% of DCIS-Mi and was confined exclusively in Van Nuys DCIS group 2 and 3. In ADH and IDH, no expression of p53 protein was found. There was no significant correlation between Van Nuys DCIS groups and Ki-67 LI. In conclusion, p53 mutation may be involved in the neoplastic progression from ADH to DCIS and is directly related to high nuclear grade and associated necrosis of DCIS.

Case Report

Borderline Clear Cell Adenofibromatous Tumors of the Ovary: Two Case Reports.: Heejeong Lee, Tae Jung Kim, Jeana Kim, Eun Joo Seo, Kyo Young Lee; Korean J Pathol. 2007;41(6):420-423.

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Abstract PDF: Borderline clear cell adenofibromatous tumors are rare with only 26 cases reported in the English literature. Five of these cases exhibited microinvasion and 4 demonstrated intraepithelial carcinoma. We report 2 cases, one typical case and the other with microinvasion. The histological findings revealed widely spaced and focally crowded, variably-sized atypical glands or tubules lined by clear, eosinophilic or hobnail cells set in a dense fibrous stroma. One of the two cases had small solid nests or single cells in the stroma around the proliferative glands less than 1 mm in length that was considered to be a microinvasion.

Original Article

Immunohistochemical Analysis of Transforming Growth Factor-beta Expression in Gastric Adenocarcinoma.: Young Hee Choi, Seoung Wan Chae, Min Chul Lee, Jung Weon Shim, Hye Kyung Ahn, Hye Rim Park, Gu Kang, Hyung Sik Shin, Young Euy Park; Korean J Pathol. 1994;28(3):272-281.

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Abstract: Thirty cases of gastric adenocarcinoma were examined immunohistochemically for expression of transforming growth factor-beta(TGF-beta) in order to analyze significant correlation with clinical stage and pathologic grade of gastric adenocarcinoma. Specific immunostaining was clearly detected in the cytoplasm of the neoplastic cells. The TGF-,6 expression in the gastric adenocarcinoma is closely related to the depth of invasion, the degree of invasiveness and the presence of metastasis. Thus, we observed the stronger immunohistochemical. expression of TGF-beta in the deeper portion of invasion and in the invasive gastric adenocarcinomas with the lymph nodal metastasis than in the superficial portion of invasion and in those without the lymph nodal metastasis. There results suggest that the transforming growth factors expression in carcinoma cells may play an important role in the carcinomatous invasion resulting in metastasis.

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