Journal of Pathology and Translational Medicine

Original Articles

Loss of Nuclear BAP1 Expression Is Associated with High WHO/ISUP Grade in Clear Cell Renal Cell Carcinoma: Young Chan Wi, Ahrim Moon, Min Jung Jung, Yeseul Kim, Seong Sik Bang, Kiseok Jang, Seung Sam Paik, Su-Jin Shin; J Pathol Transl Med. 2018;52(6):378-385. Published online October 1, 2018; DOI: https://doi.org/10.4132/jptm.2018.09.21

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Background
BRCA1-associated protein 1 (BAP1) mutations are frequently reported in clear cell renal cell carcinoma (ccRCC); however, very few studies have evaluated the role of these mutations in other renal cell carcinoma (RCC) subtypes. Therefore, we analyzed BAP1 protein expression using immunohistochemistry in several RCC subtypes and assessed its relationship with clinicopathological characteristics of patients.
Methods
BAP1 expression was immunohistochemically evaluated in tissue microarray blocks constructed from 371 samples of RCC collected from two medical institutions. BAP1 expression was evaluated based on the extent of nuclear staining in tumor cells, and no expression or expression in < 10% of tumor cells was defined as negative.
Results
Loss of BAP1 expression was observed in ccRCC (56/300, 18.7%), chromophobe RCC (6/26, 23.1%), and clear cell papillary RCC (1/4, 25%), while we failed to detect BAP1 expression loss in papillary RCC, acquired cystic disease-associated RCC, or collecting duct carcinoma. In ccRCC, loss of BAP1 expression was significantly associated with high World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grade (p = .002); however, no significant correlation was observed between loss of BAP1 expression and survival in ccRCC. Loss of BAP1 expression showed no association with prognostic factors in chromophobe RCC.
Conclusions
Loss of BAP1 nuclear expression was observed in both ccRCC and chromophobe RCC. In addition, BAP1 expression loss was associated with poor prognostic factors such as high WHO/ISUP grade in ccRCC.

Citations

Citations to this article as recorded by

Clinical and Genomic Features of Patients with Renal Cell Carcinoma and Advanced Chronic Kidney Disease: Analysis of a Multi-Institutional Database
Corbin J. Eule, Junxiao Hu, Dale Hedges, Alkesh Jani, Thomas Pshak, Brandon J. Manley, Alejandro Sanchez, Robert Dreicer, Zin W. Myint, Yousef Zakharia, Elaine T. Lam
Cancers.2024; 16(10): 1920. CrossRef
Immune regulation and prognosis indicating ability of a newly constructed multi-genes containing signature in clear cell renal cell carcinoma
Ziwei Gui, Juan Du, Nan Wu, Ningning Shen, Zhiqing Yang, Huijun Yang, Xuzhi Wang, Na Zhao, Zixin Zeng, Rong Wei, Wenxia Ma, Chen Wang
BMC Cancer.2023;[Epub] CrossRef
Radiogenomic Associations Clear Cell Renal Cell Carcinoma: An Exploratory Study
Derek H Liu, Komal A Dani, Sharath S Reddy, Xiaomeng Lei, Natalie L Demirjian, Darryl H Hwang, Bino A Varghese, Suhn Kyong Rhie, Felix Y. Yap, David I. Quinn, Imran Siddiqi, Manju Aron, Ulka Vaishampayan, Haris Zahoor, Steven Y Cen, Inderbir S Gill, Vinay
Oncology.2023; 101(6): 375. CrossRef
Immunohistochemistry for the diagnosis of renal epithelial neoplasms
Mahmut Akgul, Sean R Williamson
Seminars in Diagnostic Pathology.2022; 39(1): 1. CrossRef
BRCA1-Associated Protein 1 (BAP-1) as a Prognostic and Predictive Biomarker in Clear Cell Renal Cell Carcinoma: A Systematic Review
Shuchi Gulati, Melissa Previtera, Primo N. Lara
Kidney Cancer.2022; 6(1): 23. CrossRef
Renal Cell Carcinoma in End-Stage Renal Disease: A Review and Update
Ziad M. El-Zaatari, Luan D. Truong
Biomedicines.2022; 10(3): 657. CrossRef
CD117, BAP1, MTAP, and TdT Is a Useful Immunohistochemical Panel to Distinguish Thymoma from Thymic Carcinoma
Mounika Angirekula, Sindy Y Chang, Sarah M. Jenkins, Patricia T. Greipp, William R. Sukov, Randolph S. Marks, Kenneth R. Olivier, Stephen D. Cassivi, Anja C Roden
Cancers.2022; 14(9): 2299. CrossRef
BAP1 in cancer: epigenetic stability and genome integrity
Sabrina Caporali, Alessio Butera, Ivano Amelio
Discover Oncology.2022;[Epub] CrossRef
Bioinformatic analysis identifying FGF1 gene as a new prognostic indicator in clear cell Renal Cell Carcinoma
Xiaoqin Zhang, Ziyue Wang, Zixin Zeng, Ningning Shen, Bin Wang, Yaping Zhang, Honghong Shen, Wei Lu, Rong Wei, Wenxia Ma, Chen Wang
Cancer Cell International.2021;[Epub] CrossRef
Identification of Four Pathological Stage-Relevant Genes in Association with Progression and Prognosis in Clear Cell Renal Cell Carcinoma by Integrated Bioinformatics Analysis
Dengyong Xu, Yuzi Xu, Yiming Lv, Fei Wu, Yunlong Liu, Ming Zhu, Dake Chen, Bingjun Bai
BioMed Research International.2020; 2020: 1. CrossRef
Functional characterisation guides classification of novel BAP1 germline variants
Jing Han Hong, Siao Ting Chong, Po-Hsien Lee, Jing Tan, Hong Lee Heng, Nur Diana Binte Ishak, Sock Hoai Chan, Bin Tean Teh, Joanne Ngeow
npj Genomic Medicine.2020;[Epub] CrossRef
Tissue-Based Immunohistochemical Markers for Diagnosis and Classification of Renal Cell Carcinoma
Liang G Qu, Vaisnavi Thirugnanasundralingam, Damien Bolton, Antonio Finelli, Nathan Lawrentschuk
Société Internationale d’Urologie Journal.2020; 1(1): 68. CrossRef
Radiogenomics: bridging imaging and genomics
Zuhir Bodalal, Stefano Trebeschi, Thi Dan Linh Nguyen-Kim, Winnie Schats, Regina Beets-Tan
Abdominal Radiology.2019; 44(6): 1960. CrossRef

Expression of CD99 in Multiple Myeloma: A Clinicopathologic and Immunohistochemical Study of 170 Cases: Su-Jin Shin, Hyangsin Lee, Geunyoung Jung, Minchan Gil, Hosub Park, Young Soo Park, Dok Hyun Yoon, Cheolwon Suh, Chan-Jeoung Park, Jooryung Huh, Chan-Sik Park; Korean J Pathol. 2014;48(3):209-216. Published online June 26, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.3.209

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Abstract PDF

Background

Multiple myeloma (MM) is a heterogeneous and ultimately fatal disease. Risk stratification using prognostic biomarkers is crucial to individualize treatments. We sought to investigate the role of CD99, a transmembrane protein highly expressed in many hematopoietic cells including subpopulations of normal and neoplastic plasma cells, for MM risk stratification.

Methods

CD99 expression was measured in paraffin samples of bone marrow and extramedullary biopsies of 170 patients with MM. Patients were divided into those with high score (moderately and strongly positive) and low score (negative and weakly positive), with all staining being cytoplasmic and/or membranous.

Results

High anti-CD99 immunostaining was observed in 72 of 136 (52.9%) bone marrow biopsies and 24 of 87 (27.6%) extramedullary biopsies in MM. High CD99 expression of extramedullary specimens was associated with significantly longer overall survival (OS; p=.016). High CD99 expression of extramedullary specimens was also associated with better prognosis in the nonautologous stem cell transplantation group of MM patients (p=.044). In multivariate analysis, International Staging System stage was an independent prognostic factor, whereas CD99 expression was no longer statistically significant.

Conclusions

Expression of CD99 in extramedullary specimens was correlated with longer OS, suggesting that CD99 may be a helpful immunohistochemical marker for risk stratification.

Citations

Citations to this article as recorded by

Cell Adhesion Molecule CD99 in Cancer Immunotherapy
Feng Yu, Guodong Liu, Hailing Zhang, Xiaoyan Wang, Zhi Wu, Qinggang Xu, Yan Wu, Dongfeng Chen
Current Molecular Medicine.2023; 23(10): 1028. CrossRef
Detection of Circulating Tumor Plasma Cells in Monoclonal Gammopathies: Methods, Pathogenic Role, and Clinical Implications
Luzalba Sanoja-Flores, Juan Flores-Montero, Martín Pérez-Andrés, Noemí Puig, Alberto Orfao
Cancers.2020; 12(6): 1499. CrossRef
Tumor suppressor CD99 is downregulated in plasma cell neoplasms lacking CCND1 translocation and distinguishes neoplastic from normal plasma cells and B-cell lymphomas with plasmacytic differentiation from primary plasma cell neoplasms
Qi Gao, Venkata Yellapantula, Maly Fenelus, Janine Pichardo, Lu Wang, Ola Landgren, Ahmet Dogan, Mikhail Roshal
Modern Pathology.2018; 31(6): 881. CrossRef
EWSR1 fusion proteins mediate PAX7 expression in Ewing sarcoma
Gregory W Charville, Wei-Lien Wang, Davis R Ingram, Angshumoy Roy, Dafydd Thomas, Rajiv M Patel, Jason L Hornick, Matt van de Rijn, Alexander J Lazar
Modern Pathology.2017; 30(9): 1312. CrossRef
Activation of the polycomb repressive complex pathway in the bone marrow resident cells of diffuse large B-cell lymphoma patients
Eun Ji Oh, Eun Kyung Kim, Woo Ick Yang, Sun Och Yoon
Leukemia & Lymphoma.2016; 57(8): 1921. CrossRef
CD99 Is Strongly Expressed in Basal Cells of the Normal Adult Epidermis and Some Subpopulations of Appendages: Comparison with Developing Fetal Skin
Gawon Choi, Jin Roh, Chan-Sik Park
Journal of Pathology and Translational Medicine.2016; 50(5): 361. CrossRef
Towards Stratified Medicine in Plasma Cell Myeloma
Philip Egan, Stephen Drain, Caroline Conway, Anthony Bjourson, H. Alexander
International Journal of Molecular Sciences.2016; 17(10): 1760. CrossRef
Human Myeloma Cell Lines Induce Osteoblast Downregulation of CD99 Which Is Involved in Osteoblast Formation and Activity
Angela Oranger, Giacomina Brunetti, Claudia Carbone, Graziana Colaianni, Teresa Mongelli, Isabella Gigante, Roberto Tamma, Giorgio Mori, Adriana Di Benedetto, Marika Sciandra, Selena Ventura, Katia Scotlandi, Silvia Colucci, Maria Grano
Journal of Immunology Research.2015; 2015: 1. CrossRef
CD99 regulates CXCL12-induced chemotaxis of human plasma cells
Minchan Gil, Hyo-Kyung Pak, A-Neum Lee, Seo-Jung Park, Yoonkyung Lee, Jin Roh, Hyunji Lee, Yoo-Sam Chung, Chan-Sik Park
Immunology Letters.2015; 168(2): 329. CrossRef

Expression of p53 Protein and c-erbB-2 Oncoprotein in Breast Carcinoma.: Eun Hee Lee, Dong Sug Kim, Tae Sook Lee, Soo Jung Lee; Korean J Pathol. 1995;29(5):596-606.

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Abstract: This study was conducted to evaluate the expression of p53 and c-erbB-2 using immuno-histochemical methods in 145 primary breast carcinomas and to correlate it with other histo-pathological prognostic factors. Invasive ductal carcinoma represented 129 of the cases. Expression of p53 protein and c-erbB-2 oncoprotein was present in 48% (62/129) and 30% (39/129) of invasive ductal carcinomas, respectively. The expression of p53 protein was stongly associated with a high score of degree of differentiation (p<0.05), nuclear pleomorphism (p<0.05), mitotic index (p<0.05), SBR grade (p<0.05) and MSBR grade (p<0.05), but it was not associated with patient's age, size of tumor or axillary node metastasis. The overexpression of c-erbB-2 C-erbB-2 oncoprotein was strongly associated with a high score of nuclear pleomorphism and a high SBR grade (p<0.05), but not associated with patient's age, size of tumor, axillary node metastasis, degree of differentiation, mitotic index or MSBR grade. An inverse relationship between the expression of p53 protein and estrogen receptor status was found, but the expression of c-erbB-2 was not associated with estrogen receptor status. It is concluded that p53 protein and c-erbB-2 oncoprotein are important prognostic factors in breast cancers, and that the aberrant expression of p53 protein is the most useful prognostic factor becausd of strong association of known histopathological prognostic factors and negative estrogen receptor status.

Immunohistochemical Analysis of HLA-DR and Secretory Component Expression in Gastric Adenocarcinoma.: Ji Youn Bae, Soo Sang Sohn, Eun Sook Chang; Korean J Pathol. 1996;30(4):293-300.

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Abstract PDF: Sixty one cases of gastric adenocarcinoma were studied immunohistochemically for expression of HLA-DR and secretory component(SC) in order to analyze the relationship between expression of these in gastric cancer cells and the adjacent mucosa. Immunostaining was detected within the cytoplasm and on the cell memgrane. The rate of HLA-DR and SC expressions in cancer cells were 59.0% and 49.2%, respectively, and 52.5%/52.5% and 31.2%/50.8% the mucosa in adjacent/remote from the site of to cancer. The SC expression in the adjacent mucosa was lower than that of the remote mucosa(p=0.027). The HLA-DR expression in the cancer cells in the intestinal type of gastric adenocarcinoma(73.9%) was higher than that of the diffuse type(14.3%) and it was statistically significant(p=0.02). The presence of an increased amount of lymphoid infiltration in the gastric mucosa was closely related to the expression of HLA-DR and SC. Decreased or absent expression of SC at the transitional mucosal cells was possibly a result of exposure to genotoxic agents due to the lack of protective function of SC-IgA. From these results, one can postulate that the expression of HLA-DR and SC may play an important role in atleration in microenvironment with lymphoid infiltration.

Case Report

Creutzfeldt-Jakob Disease: Histopathologic, Electron Microscopic and Immunohistochemical Studies of 2 Cases.: Duck Hwan Kim, Yeon Lim Suh, Duck Ryul Na, Won Kyu Joo, Yong Sun Kim; Korean J Pathol. 1996;30(9):830-838.

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Abstract PDF: Creutzfeldt-Jakob disease(CJD) is characterized clinically by rapidly progressive dementia with pyramidal, extrapyramidal, and cerebellar symptoms and signs, and histologically by spongiform change, neuronal loss and reactive gliosis. We have experienced 2 cases of CJD. Case 1 was a 36-year-old male who had suffered from myoclonus and cerebellar symptoms including sluggish speech, gait and balance disturbance. Case 2 was a 70-year-old female who had showed cognitive dysfunction, ataxic gait and disturbance of extraocular movement. Both patients, underwent brain biopsy.
Case
1 revealed marked cortical atrophy, 2mm in thickness, with neuronal loss and astrocytic proliferation extending into white matter. The spongiform change, made up of many small, usually rounded or oval, vacuoles was noted mainly in the neuropil. Case 2 revealed remarkable spongiform change throughout the cortex and cytoplasmic vacuoles compressing the nuclei of neuronal cells were numerous. Neuronal loss and gliosis were also found without considerable change in the white matter. On double immunostaining against GFAP and PrP(Prion Protein), there was a weak positive reaction for PrP in the perinuclear cytoplasm in case 1, and a strongly positive reaction in case 2. The electron microscopic examination showed numerous membrane-bound vacuoles in neuropil and perikarya of neurons. The majority of the vacuoles were multiseptated by thin membranous structures. They demonstrated curled, or disrupted membrane, that had foldings and protrusions into the vacuolar clear spaces. There were neither identifiable virus-like particles nor amyloid deposition.

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