Deletion status of p16 in effusion smear preparation correlates with that of underlying malignant pleural mesothelioma tissue

Our plain-English summary of Deletion status of p16 in effusion smear preparation correlates with that of underlying malignant pleural mesothelioma tissue, by T. Hida, S. Matsumoto, M. Hamasaki, et al (Cancer Science, 2015).

The study

• Authors: T. Hida, S. Matsumoto, M. Hamasaki, K. Kawahara, T. Tsujimura, K. Hiroshima, T. Kamei, K. Taguchi, A. Iwasaki, Y. Oda, H. Honda, K. Nabeshima
• Journal: Cancer Science
• Published: 2015;106(11):1635-41
• Cited by: 33 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Differentiating malignant pleural mesothelioma (MPM) cells morphologically from reactive mesothelial hyperplasia cells is problematic. Homozygous deletion (HD) of p16 (CDKN2A), detected by FISH, is a good marker of malignancy and is useful to differentiate between these cells. However, the correlation between the p16 status of effusion smears and that of the underlying MPM tissues has not been investigated. We used p16-specific FISH to investigate 20 cases of MPM from which both effusion cytologic smears and histologic specimens were available. In five cases, histologic specimens included both an invasive component and surface mesothelial proliferation. In 14 cases (70%), MPM cells in both tissue sections and effusion smears were p16 HD-positive. Conversely, MPM cells in the remaining six tumors (30%) were p16 HD-negative in both tissue sections and effusion smears. For all five MPM cases with surface mesothelial proliferations and invasive components, the effusion smears, surface mesothelial proliferations, and invasive MPM components all displayed p16 deletion. Moreover, the extent to which p16 was deleted in smears highly correlated with the extent of p16 deletion in tissues. The p16 deletion percentages were also similar among smears, tissue surface proliferations, and invasive components. In cases with clinical and radiologic evidence of a diffuse pleural tumor, detection of p16 deletion in cytologic smear samples may permit MPM diagnosis without additional tissue examination. However, the absence of p16 deletion in cytologic smear samples does not preclude MPM.

© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

In plain English

This laboratory study looked at 20 patients with epithelioid malignant pleural mesothelioma (MPM) from Fukuoka University Hospital pathology files in Japan, 2007 to 2013. Each had both fluid (effusion) smears and tissue samples. The authors used a genetic test, FISH, to look for loss of both copies of the p16 gene (homozygous deletion). A sample counted as positive when more than 10% of mesothelial cells showed this loss, a cut-off set using benign mesothelial samples from other patients. Asbestos exposure was not studied. Fourteen of the 20 patients (70%) showed the deletion in both smear and tissue; the other six (30%) showed it in neither. Smear and tissue shares of affected cells closely matched (coefficient of determination 0.9528). All five cases with three sample types showed the deletion. The smear-to-tissue correlations in those five were not statistically significant (P = 0.1041). The authors concluded that smear p16 deletion may permit diagnosis without further tissue examination when clinical and radiologic evidence shows a diffuse pleural tumor, though its absence does not rule out MPM. They noted the small number of cases.

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 comparing a genetic test (p16 FISH) on matched effusion cytology smears and tissue specimens from mesothelioma cases in hospital pathology files
• Who was studied: 20 patients with malignant pleural mesothelioma (17 male, 3 female; mean age 66.6 years, range 55 to 81; all epithelioid subtype) from the pleural lesion files of the Department of Pathology, Fukuoka University Hospital, Japan, including consultation cases, 2007 to 2013. Five of the 20 had tissue showing both surface mesothelial proliferation and invasive tumor. To set the test cut-off, the authors also used cytology from 28 non-mesothelioma cases with reactive mesothelial cells and tissue from 25 cases with reactive mesothelial hyperplasia.
• Exposure: Asbestos exposure was not studied. The study measured homozygous deletion of the p16 (CDKN2A) gene by FISH in effusion smears and tissue.
• Main results:
  • A case was counted as p16 homozygous deletion-positive when the deletion was found in more than 10% of mesothelial cells, with at least 100 cells scored per case. In the benign comparison samples, the homozygous deletion pattern was seen in 0 to 3.6% of cells (mean 1.3%) in cytology with reactive mesothelial cells and in 0.8 to 4.7% (mean 2.6%) in tissue with reactive mesothelial hyperplasia.
  • 14 of the 20 patients (70%) showed p16 homozygous deletion in both the MPM tissue and the atypical mesothelial cells in effusion smears.
  • The remaining 6 of 20 patients (30%) were p16 deletion-negative in both tissue and smears. No case had a mismatch between smear and tissue results.
  • Among the 14 deletion-positive cases, more than 90% of tumor cells showed deletion in 12 cases. In the other 2 cases, only 10 to 30% of cells showed it, in both smear and tissue.
  • Across all 20 cases, the percentage of deleted cells in smears closely matched the percentage in tissue in a simple linear regression (coefficient of determination 0.9528).
  • All 5 cases with smears, surface proliferations and invasive tumor were deletion-positive, with similar rates in all three sample types. The authors called the correlation a trend because the number of cases was not enough. Smears vs surface tissue and smears vs invasive tissue each gave a Spearman coefficient of 0.8000 with P = 0.1041, which is not statistically significant. Surface vs invasive tissue gave 1.0000 with P less than 0.0001.
• The authors' conclusion: The authors concluded that p16 FISH is a powerful tool to tell MPM apart from benign mesothelial proliferations. They also concluded that finding p16 deletion in smears may permit an MPM diagnosis without further tissue examination when there is clinical and radiologic evidence of a diffuse pleural tumor. However, absence of the deletion in smears does not exclude MPM.
• Limitations the authors state:
  • The number of cases was relatively small, especially the cases with all three sample types, which was too few to reach statistical significance.
  • Lack of p16 deletion in effusion tumor cells does not rule out MPM, because some mesotheliomas do not show the deletion.
  • p16 deletion status cannot separate MPM from mesothelioma-like metastases of other cancers, such as carcinomas of the lung, bladder, breast and prostate.
  • Only epithelioid MPMs were included.
  • Some MPMs, such as the sarcomatoid subtype, occur without pleural effusion and cannot be diagnosed by effusion cytology.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma, Pleural plaques and thickening.

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

Related studies

• Use of p16 FISH for differential diagnosis of mesothelioma in smear preparations — K. Nabeshima, S. Matsumoto, et al. (2016)
• 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)
• 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)
• Morphological difference between pleural mesothelioma cells in effusion smears with either BAP1 loss or 9p21 homozygous deletion and reactive mesothelial cells without the gene alterations — S. Matsumoto, M. Hamasaki, et al. (2019)
• p16 FISH deletion in surface epithelial mesothelial proliferations is predictive of underlying invasive mesothelioma — H. Hwang, C. Tse, et al. (2014)
• A combination of MTAP and BAP1 immunohistochemistry in pleural effusion cytology for the diagnosis of mesothelioma — Y. Kinoshita, T. Hida, et al. (2018)

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