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

Am J Clin Pathol. 2015 Jun;143(6):830-8. doi: 10.1309/AJCPOATJ9L4GCGDA.

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.

Keywords: 9p21; Diffuse malignant peritoneal mesothelioma; Epithelial ovarian cancer; Fluorescence in situ hybridization; Reactive mesothelial hyperplasia; p16.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Carcinoma, Ovarian Epithelial
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Diagnosis, Differential*
  • Female
  • Genes, p16*
  • Humans
  • Hyperplasia / diagnosis
  • Hyperplasia / genetics
  • In Situ Hybridization, Fluorescence
  • Male
  • Mesothelioma / diagnosis*
  • Mesothelioma / genetics
  • Middle Aged
  • Neoplasms, Glandular and Epithelial / diagnosis*
  • Neoplasms, Glandular and Epithelial / genetics
  • Ovarian Neoplasms / diagnosis*
  • Ovarian Neoplasms / genetics
  • Peritoneal Neoplasms / diagnosis*
  • Peritoneal Neoplasms / genetics
  • Precancerous Conditions / diagnosis
  • Precancerous Conditions / genetics
  • Sensitivity and Specificity

Substances

  • Biomarkers, Tumor
  • Cyclin-Dependent Kinase Inhibitor p16