p16 FISH deletion in surface epithelial mesothelial proliferations is predictive of underlying invasive mesothelioma

Our plain-English summary of p16 FISH deletion in surface epithelial mesothelial proliferations is predictive of underlying invasive mesothelioma, by H. Hwang, C. Tse, S. Rodriguez, et al (The American Journal of Surgical Pathology, 2014).

The study

• Authors: H. Hwang, C. Tse, S. Rodriguez, A. Gown, A. Churg
• Journal: The American Journal of Surgical Pathology
• Published: 2014;38(5):681-8
• Cited by: 31 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

An atypical mesothelial proliferation along the pleural or peritoneal surface without evidence of invasive tumor poses a diagnostic challenge. Homozygous deletion of p16 (CDKN2A) by fluorescence in situ hybridization (FISH) has been shown to be a good marker of malignancy in mesothelial proliferations, but correlations of p16 status between atypical surface proliferations and underlying mesothelioma have not been described. We used p16 FISH to investigate 11 pleural and 7 peritoneal mesotheliomas that had both an invasive component and a separate surface mesothelial proliferation. In 5/11 pleural samples and 1/7 peritoneal samples, the invasive mesotheliomas showed homozygous deletion of p16 (all cases in excess of 90% of cells deleted); the surface proliferation in all 6 cases with deletion in the invasive tumor was also p16 deleted. Conversely, the 12 tumors that did not show p16 deletion in the invasive compartment also did not have deletion in the surface component. We conclude that (1) surface mesothelial proliferations near invasive mesotheliomas show the same pattern of p16 by FISH as the underlying tumor and may represent in situ disease or growth of the underlying mesothelioma along the serosal surface; (2) p16 deletion in mesothelial surface proliferations is strongly associated with p16 deletion in underlying mesotheliomas, and biopsies consisting of pure surface mesothelial proliferations that are p16 deleted allow a diagnosis of mesothelioma without an additional biopsy if there is clinical (thoracosopic/laparoscopic) or radiologic evidence of diffuse pleural or peritoneal tumor; (3) however, the absence of p16 deletion in surface proliferations does not rule out underlying invasive mesothelioma.

In plain English

This laboratory study asked whether a genetic test could help diagnose mesothelioma from biopsies showing only abnormal mesothelial cells growing on the surface of the pleura or peritoneum, without invasion. The authors took 18 cases of epithelial malignant mesothelioma (11 pleural, 7 peritoneal) from one author's consultation files. Each case had both invasive tumor and a separate surface growth. The authors used FISH testing to look for homozygous deletion of the p16 (CDKN2A) gene. The invasive tumor showed deletion in 5 of 11 pleural and 1 of 7 peritoneal cases, and in all 6 of these the surface growth was also deleted. In the other 12 cases, neither part showed deletion. Biopsies from 2 further patients had only surface growth, although tumor was seen on the pleura at thoracoscopy. Both biopsies showed deletion. The authors concluded that p16 deletion in a surface growth can allow a mesothelioma diagnosis without another biopsy when clinical or radiologic evidence shows diffuse tumor. They added that absence of deletion does not rule out mesothelioma. They noted their sample was small. The article did 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: Retrospective laboratory (pathology) study of archived biopsy specimens tested by p16 FISH, plus 2 additional illustrative patient biopsies
• Who was studied: 18 cases of epithelial malignant mesothelioma (11 pleural, 7 peritoneal) from the consultation files of one author (A.C.), each with invasive tumor and a separate surface mesothelial proliferation; plus biopsies from 2 patients with pleural tumor at thoracoscopy whose biopsies showed only a surface proliferation
• Main results:
  • Homozygous p16 deletion was found in the invasive component of 5/11 (45.5%) pleural mesotheliomas
  • Across pleural and peritoneal cases combined, deletion was found in 6 of 18 tumors (33.3%); this included 1 of 7 peritoneal cases (14.3%)
  • In the 6 deleted cases, more than 90% of invasive tumor cells were deleted, and the surface component of the same 6 cases was also deleted, with more than 85% of cells deleted
  • In the remaining 12 cases, neither the invasive tumor nor the surface component showed deletion, giving 100% concordance between the two components
  • In the 2 additional patients whose biopsies showed only a surface proliferation, 100% and 92% of nuclei showed p16 deletion; the first patient died of tumor 4 months after biopsy, with mesothelioma confirmed at autopsy, and the second was alive 12 months after biopsy
• The authors' conclusion: The authors concluded that p16 FISH can be useful when a biopsy shows only a surface mesothelial proliferation, and that deletion allows a diagnosis of mesothelioma without another biopsy if there is compatible clinical or radiologic evidence of diffuse serosal tumor. They suggested the surface growth may be invasive tumor that has grown onto the surface rather than true in situ disease.
• Limitations the authors state:
  • Many surface proliferations were not p16 deleted despite underlying invasive tumor, so absence of deletion does not mean the process is benign
  • The sensitivity of p16 FISH may limit its use; the peritoneal tumors showed a lower frequency of deletion than the pleural tumors
  • The number of samples examined was relatively small
  • The authors did not propose using p16 FISH to detect pure mesothelioma in situ without underlying invasive tumor

Topics

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

Medical terms in this study, explained in our Lexicon: Fluorescence In Situ Hybridization (FISH), Mesothelioma, Atypical Mesothelial Proliferation, Homozygous Deletion, CDKN2A, Peritoneal Mesothelioma, Serosal Surface, Biopsy.

Related studies

• p16/CDKN2A FISH in Differentiation of Diffuse Malignant Peritoneal Mesothelioma From Mesothelial Hyperplasia and Epithelial Ovarian Cancer — T. Ito, M. Hamasaki, et al. (2015)
• FISH assay development for the detection of p16/CDKN2A deletion in malignant pleural mesothelioma — C.T. Chung, C. Santos Gda, et al. (2010)
• Low homozygous/high heterozygous deletion status by p16 FISH correlates with a better prognostic group than high homozygous deletion status in malignant pleural mesothelioma — M. Hamasaki, S. Matsumoto, et al. (2016)
• Deletion status of p16 in effusion smear preparation correlates with that of underlying malignant pleural mesothelioma tissue — T. Hida, S. Matsumoto, et al. (2015)
• BAP1 immunohistochemistry and p16 FISH to separate benign from malignant mesothelial proliferations — B.S. Sheffield, H.C. Hwang, et al. (2015)
• Fluorescence in situ hybridization (FISH) provides estimates of minute and interstitial BAP1, CDKN2A, and NF2 gene deletions in peritoneal mesothelioma — S. Brich, F. Bozzi, et al. (2020)

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