p16/CDKN2A FISH in Differentiation of Diffuse Malignant Peritoneal Mesothelioma From Mesothelial Hyperplasia and Epithelial Ovarian Cancer

Our plain-English summary of p16/CDKN2A FISH in Differentiation of Diffuse Malignant Peritoneal Mesothelioma From Mesothelial Hyperplasia and Epithelial Ovarian Cancer, by T. Ito, M. Hamasaki, S. Matsumoto, et al (American Journal of Clinical Pathology, 2015).

The study

• Authors: T. Ito, M. Hamasaki, S. Matsumoto, K. Hiroshima, T. Tsujimura, T. Kawai, Y. Shimao, K. Marutsuka, S. Moriguchi, R. Maruyama, S. Miyamoto, K. Nabeshima
• Journal: American Journal of Clinical Pathology
• Published: 2015;143(6):830-8
• Cited by: 31 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objectives: It can be difficult to differentiate diffuse malignant peritoneal mesothelioma (DMPM) from reactive mesothelial hyperplasia (RMH) or peritoneal dissemination of gynecologic malignancies, such as epithelial ovarian cancer (EOC), which cause a large amount of ascites. Detection of the homozygous deletion of p16/CDKN2A (p16) by fluorescence in situ hybridization (FISH) is an effective adjunct in the diagnosis of malignant pleural mesothelioma. The aim of this study was to investigate the ability of the p16 FISH assay to differentiate DMPM from RMH and EOC.

Methods: p16 FISH was performed in 28 DMPMs (successful in 19), 30 RMHs, and 40 EOC cases. The cutoff values of p16 FISH were more than 10% for homozygous deletion and more than 40% for heterozygous deletion.

Results: According to the above criteria, nine (47.4%) of 19 successful DMPM cases were homozygous deletion positive, and three (15.8%) of 19 were heterozygous deletion positive, whereas all RMH cases were negative for the p16 deletion. In all four major histologic subtypes of EOC, neither p16 homozygous nor heterozygous deletions were detected. To differentiate DMPM from RMH or EOC, the sensitivity of the p16 homozygous deletion was 32% (9/28), and the specificity was 100%.

Conclusions: Our study suggests that p16 FISH analysis is useful in differentiating DMPM from RMH and EOC when homozygous deletion is detected.

Copyright© by the American Society for Clinical Pathology.

In plain English

This laboratory study, by pathologists in Japan, tested whether a genetic test called p16 FISH could tell diffuse malignant peritoneal mesothelioma (DMPM), a cancer of the abdominal lining, apart from reactive mesothelial hyperplasia (RMH), a non-cancerous change in that lining, and epithelial ovarian cancer (EOC). The authors tested stored tissue from 28 DMPM cases, 40 EOC cases and 30 RMH cases. The cases came from Fukuoka University Hospital files covering August 1993 through January 2012. The test worked in 19 of the 28 DMPM cases and failed more often in autopsy samples. Loss of both copies of the p16 gene (homozygous deletion) was found in 9 of 28 DMPM cases, which was 9 of the 19 successfully tested. It was found in none of the RMH or EOC cases. The test's sensitivity was 32% (9/28) and its specificity was 100%. The authors concluded that the deletion is a useful tool to confirm DMPM over RMH or EOC, but that its absence cannot rule out DMPM. They said more EOC cases need study. The article does not discuss asbestos exposure.

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: Laboratory diagnostic study of archived tissue samples (fluorescence in situ hybridization testing of stored pathology specimens)
• Who was studied: Tissue from 28 diffuse malignant peritoneal mesothelioma cases (14 men, 14 women; mean age 65.1 years), 40 epithelial ovarian cancer cases (all women; mean age 52.9 years) and 30 reactive mesothelial hyperplasia cases (all women; mean age 50.1 years). The cases came from Fukuoka University Hospital files and consultation cases in Japan, August 1993 through January 2012.
• Exposure: No asbestos or other exposure was studied. The study examined a laboratory test: p16/CDKN2A fluorescence in situ hybridization (FISH), which looks for loss of the p16 gene in tissue cells.
• Main results:
  • The p16 FISH test was successful in 19 of 28 DMPM cases (67.9%)
  • Among the 9 DMPM autopsy samples, the test succeeded in 3 (33.3%) and failed in 6 (66.7%)
  • Homozygous p16 deletion was found in 9 of 28 DMPM cases (32%). This was 9 of the 19 DMPM cases with successful FISH (47.4%).
  • Three DMPM cases were heterozygous deletion positive, and all three were also homozygous deletion positive
  • All 30 RMH cases were negative for p16 deletion
  • None of the 40 EOC cases was positive for homozygous or heterozygous p16 deletion
  • Homozygous deletions were significantly more frequent in all DMPM cases, and in female-only DMPM cases, than in RMH cases (P less than .05)
  • Homozygous deletion was significantly more frequent in female DMPM cases than in EOC cases (P less than .05)
  • For telling DMPM apart from RMH or EOC, homozygous p16 deletion had a sensitivity of 32% (9/28) and a specificity of 100%
• The authors' conclusion: The authors concluded that p16 homozygous deletion is a useful tool to confirm that a case is DMPM rather than RMH or EOC. They added that where the deletion is lacking, a diagnosis of DMPM cannot be ruled out.
• Limitations the authors state:
  • Small numbers of EOC cells showed p16 deletion (mean 7.9%, range 2.8% to 9.6%). These cases were counted as negative only because they fell below the 10% cutoff.
  • As more EOC cases are tested, homozygous deletions above 10% might occur, so further studies with more cases are needed
  • The authors stated that p16 FISH is of no use for telling DMPM apart from pancreatic ductal adenocarcinoma or cholangiocarcinoma
  • Delay before formalin fixation in autopsy cases might explain the higher rate of FISH failures in those samples

Topics

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

Medical terms in this study, explained in our Lexicon: CDKN2A, Fluorescence In Situ Hybridization (FISH), Peritoneal Mesothelioma, Reactive Mesothelial Hyperplasia, Ovarian Cancer, Ascites, Homozygous Deletion, Pleural Mesothelioma.

Related studies

• Peritoneal malignant mesothelioma (PMM), and primary peritoneal serous carcinoma (PPSC) and reactive mesothelial hyperplasia (RMH) of the peritoneum. Immunohistochemical and fluorescence in situ hybridisation (FISH) analyses — T. Kawai, S. Tominaga, et al. (2016)
• p16 FISH deletion in surface epithelial mesothelial proliferations is predictive of underlying invasive mesothelioma — H. Hwang, C. Tse, et al. (2014)
• Value of mesothelial and epithelial antibodies in distinguishing diffuse peritoneal mesothelioma in females from serous papillary carcinoma of the ovary and peritoneum — R.L. Attanoos, R. Webb, et al. (2002)
• Use of p16 FISH for differential diagnosis of mesothelioma in smear preparations — K. Nabeshima, S. Matsumoto, et al. (2016)
• 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)

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