Evaluation of MTAP immunohistochemistry loss of expression in ovarian serous borderline tumors as a potential marker for prognosis and progression

Our plain-English summary of Evaluation of MTAP immunohistochemistry loss of expression in ovarian serous borderline tumors as a potential marker for prognosis and progression, by N. Nilforoushan, N.A. Moatamed (Annals of Diagnostic Pathology, 2020).

The study

• Authors: N. Nilforoushan, N.A. Moatamed
• Journal: Annals of Diagnostic Pathology
• Published: 2020;48:151582
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Serous borderline tumors (SBT) are the most common subtype of ovarian borderline tumors with excellent clinical course. However, they can recur or progress to low-grade serous carcinoma (LGSC) in a small proportion of the cases. Beside BRAF and KRAS mutations, copy number alterations (CNA), particularly loss of chromosome 9p21 locus which results in deletion of genes CDKN2A and MTAP, have been suggested to be involved in disease progression. MTAP immunohistochemistry recently has been introduced for mesothelioma as a reliable surrogate marker for the homozygous deletion of chromosome 9p21 locus. Therefore, in the current study, we aimed to evaluate the MTAP loss of expression in serous borderline tumors and low-grade serous carcinomas to identify if it can be used as a marker for prognosis and progression.

Method: Eighty-four total cases of ovarian serous lesions, including 21 cases of serous cystadenomas, 21 cases of serous borderline tumors, 12 cases of low-grade serous carcinomas and 30 cases of high-grade serous carcinomas were selected. MTAP immunohistochemistry was performed on the representative blocks and cytoplasmic staining was used for interpretation. The cases were labeled as positive (retained) if MTAP showed cytoplasmic granular staining and negative (loss of expression) if negative cytoplasmic staining was observed in the presence of positive internal control.

Result: Ten of 21 cases of serous borderline tumors showed loss of MTAP expression (48%). Among those, 7 cases were bilateral, 2 cases had micropapillary features, one case had supraclavicular and cervical lymph node involvement by serous borderline tumor and 2 cases had progression to low-grade serous carcinoma, including one of micropapillary tumors. Also 8 out of 12 cases of LGSCs showed MTAP loss of expression (66%). Only 4 of 30 cases of high-grade serous carcinomas (13%) and none of the serous cystadenoma cases showed loss of expression of MTAP.

Conclusion: To our knowledge, this is the first description of MTAP immunohistochemistry in serous borderline tumors and low-grade serous carcinomas. Our study was limited due to small sample size. However, it showed an association between MTAP loss of expression and adverse clinical behavior in ovarian serous borderline tumors. This supports the role for further investigations in larger series to evaluate the role of MTAP stain as a prognostic marker in these neoplasms.

Copyright © 2020. Published by Elsevier Inc.

In plain English

This study is not about asbestos and does not study mesothelioma. The authors examined tissue from 84 ovarian serous tumors, collected from the pathology archives of UCLA and Santa Monica medical centers from 2016 to 2019. They stained the tissue for a protein called MTAP, a stain that other researchers had introduced for mesothelioma. They wanted to see whether loss of MTAP could signal a worse course in serous borderline tumors. MTAP was lost in 10 of 21 serous borderline tumors (48%), 8 of 12 low-grade serous carcinomas (66%), 4 of 30 high-grade serous carcinomas (13%), and none of 21 serous cystadenomas. Among the borderline tumors, loss was seen in 5 of 7 tumors affecting both ovaries, in both tumors with micropapillary features, and in the one tumor with lymph node involvement. It was also seen in both tumors that later progressed to low-grade serous carcinoma. The authors concluded that, despite a small sample, the study showed an association between MTAP loss and adverse clinical behavior. They called for larger studies.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective laboratory study of archived tumor tissue stained for MTAP (immunohistochemistry), with stains reviewed by two pathologists unaware of stage and clinical course
• Who was studied: 84 ovarian serous lesions from UCLA and Santa Monica medical centers, 2016 to 2019: 21 serous cystadenomas, 21 serous borderline tumors, 12 low-grade serous carcinomas and 30 high-grade serous carcinomas
• Main results:
  • Serous borderline tumors: 10 of 21 showed loss of MTAP expression (48%)
  • Low-grade serous carcinomas: 8 of 12 showed MTAP loss of expression (66%)
  • High-grade serous carcinomas: 4 of 30 showed loss of MTAP expression (13%)
  • Serous cystadenomas: 0 of 21 showed loss of MTAP expression
  • Among serous borderline tumors, MTAP loss was seen in 5 of 7 bilateral tumors, in 2 of 2 tumors with micropapillary features, and in the one tumor with lymph node involvement
  • Both serous borderline tumors that progressed to low-grade serous carcinoma showed MTAP loss in both the borderline tumor and the carcinoma
• The authors' conclusion: The authors concluded that, despite a small sample size, the study showed an association between MTAP loss of expression in serous borderline tumors and adverse clinical behavior and likelihood of progression to low-grade serous carcinoma, and that larger studies are needed
• Limitations the authors state:
  • Small sample size

Topics

The National Library of Medicine indexes this study under subjects our site covers: Ovarian cancer.

Medical terms in this study, explained in our Lexicon: MTAP, Immunohistochemistry, Prognosis, Carcinoma, CDKN2A, Disease Progression, Mesothelioma, Homozygous Deletion.

Related studies

• Immunohistochemical detection of MTAP and BAP1 protein loss for mesothelioma diagnosis: Comparison with 9p21 FISH and BAP1 immunohistochemistry — T. Hida, M. Hamasaki, et al. (2017)
• CDKN2A and MTAP deletions in peritoneal mesotheliomas are correlated with loss of p16 protein expression and poor survival — A.M. Krasinskas, D.L. Bartlett, et al. (2010)
• MTAP immunohistochemistry is an accurate and reproducible surrogate for CDKN2A fluorescence in situ hybridization in diagnosis of malignant pleural mesothelioma — D.B. Chapel, J.J. Schulte, et al. (2020)
• Expression of the Ets transcription factor EHF in serous ovarian carcinoma effusions is a marker of poor survival — K. Brenne, D.A. Nymoen, et al. (2012)
• Cytokeratin 5/6 expression, prognosis, and association with estrogen receptor α in high-grade serous ovarian carcinoma — E.T. Taube, C. Denkert, et al. (2017)
• Correlation of methylthioadenosine phosphorylase (MTAP) protein expression with MTAP and CDKN2A copy number in malignant pleural mesothelioma — D.B. Chapel, A.M. Dubuc, et al. (2021)

Browse more research in Annals of Diagnostic Pathology, or return to medical research.