BAP1 Immunohistochemistry and p16 FISH in the Diagnosis of Sarcomatous and Desmoplastic Mesotheliomas

Our plain-English summary of BAP1 Immunohistochemistry and p16 FISH in the Diagnosis of Sarcomatous and Desmoplastic Mesotheliomas, by H.C. Hwang, S. Pyott, S. Rodriguez, et al (The American Journal of Surgical Pathology, 2016).

The study

• Authors: H.C. Hwang, S. Pyott, S. Rodriguez, A. Cindric, A. Carr, C. Michelsen, K. Thompson, C.H. Tse, A.M. Gown, A. Churg
• Journal: The American Journal of Surgical Pathology
• Published: 2016;40(5):714-8
• Cited by: 82 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The separation of sarcomatous and desmoplastic mesotheliomas from benign organizing pleuritis can be morphologically very difficult. Deletion of p16 (CDKN2A) by fluorescence in situ hybridization (FISH) testing appears to be a reliable marker of malignancy in mesothelial proliferations, and more recently it has been reported that, in this setting, loss of BAP1 by immunohistochemistry is only seen in malignant mesotheliomas. To determine how useful these tests are with sarcomatous and desmoplastic mesotheliomas, we examined 20 such tumors. Loss of BAP1 was seen in 3/20 (15%) and deletion of p16 by FISH was seen in 16/20 (80%) cases. Loss of one or the other marker was observed in 17/20 (85%). We also examined 13 sarcomatoid carcinomas, an important differential diagnosis of sarcomatoid mesotheliomas, and found that BAP1 was never lost, but p16 was deleted in 3/11 (27%). We conclude that: (1) BAP1 immunohistochemistry is relatively insensitive in the context of sarcomatous and desmoplastic mesotheliomas, but as a matter of time and cost efficiency may nonetheless be a useful first approach to the problem; (2) deletion of p16 by FISH is considerably more sensitive, but there remain a proportion of cases in which p16 is not deleted; (3) a small improvement in sensitivity can be achieved by using both markers; (4) in the context of a spindle cell malignant tumor in the pleura or peritoneum, which morphologically might be a metastatic sarcomatoid carcinoma or a mesothelioma, the finding of BAP1 loss favors mesothelioma, but p16 FISH cannot be used to separate sarcomatous mesotheliomas from sarcomatoid carcinomas.

In plain English

This laboratory study asked whether two tests help diagnose sarcomatous and desmoplastic mesotheliomas. These tumors can be hard to distinguish from organizing pleuritis, a benign reaction of the pleura. The authors tested tissue from 20 such pleural mesotheliomas, from 18 men and 2 women. The text gives ages of 51 to 87, but its table lists a patient aged 88. They tested for BAP1 protein loss by immunostaining and p16 (CDKN2A) gene deletion by fluorescence in situ hybridization (FISH). p16 was deleted in 16 of 20 tumors (80%), BAP1 lost in 3 of 20 (15%). One marker or the other was abnormal in 17 of 20 (85%). The authors also tested 13 sarcomatoid carcinomas, cancers that can resemble these mesotheliomas. None showed BAP1 loss; p16 was deleted in 3 of the 11 tested by FISH. The authors concluded that BAP1 loss is infrequent in these tumors, but BAP1 staining may be a good first test because it is faster and cheaper. They also concluded that BAP1 loss favors mesothelioma over carcinoma, but p16 FISH cannot separate them. The article does not discuss asbestos.

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 selected archived tumor tissue samples (mesotheliomas compared with sarcomatoid carcinomas)
• Who was studied: 20 sarcomatous or desmoplastic mesotheliomas, all pleural, from 18 male and 2 female patients, taken from one author's consultation files or Vancouver General Hospital surgical pathology files. The text gives the age range as 51 to 87, but Table 1 lists one patient (case 11) aged 88. The study also included 13 sarcomatoid carcinomas, from 9 female and 4 male patients aged 56 to 85. Of these, 5 were from the lung and 8 from other sites, and 3 were metastases. Dates of the cases are not given.
• Exposure: Not an exposure study: the article does not report asbestos or any other exposure. It evaluated two laboratory tests on tumor tissue, BAP1 immunohistochemistry and p16 (CDKN2A) FISH.
• Main results:
  • In the 20 mesotheliomas, p16 was deleted by FISH in 16/20 (80%) and BAP1 was lost by immunohistochemistry in 3/20 (15%).
  • In the mesotheliomas, 2 of the 3 tumors with BAP1 loss also had p16 deletion and 1 did not. One marker or the other was lost in 17/20 (85%).
  • Combining the two tests in the mesotheliomas raised detection only slightly, from 80% (p16 FISH alone) to 85%.
  • In the sarcomatoid carcinomas, p16 was deleted in 3/11 (27%) tested by FISH, and BAP1 was lost in 0/13 (0%).
  • The authors interpreted the absence of BAP1 loss in the sarcomatoid carcinomas as suggesting that BAP1 loss favors mesothelioma over carcinoma. They added that correlation with clinical, histologic and staining findings is still essential.
  • The authors found, in agreement with an earlier study they cite, that p16 FISH cannot accurately separate the two tumor types.
• The authors' conclusion: The authors concluded that BAP1 loss is infrequent in sarcomatous and desmoplastic mesotheliomas. They considered BAP1 immunohistochemistry a reasonable starting test because it is faster and cheaper than p16 FISH. When BAP1 is lost, it also suggests the tumor is not a sarcomatoid carcinoma.
• Limitations the authors state:
  • Because of limited material, 2 of the 13 sarcomatoid carcinomas were tested only for BAP1, not by p16 FISH.

Topics

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

Medical terms in this study, explained in our Lexicon: BAP1, Immunohistochemistry, Fluorescence In Situ Hybridization (FISH), Desmoplastic Mesothelioma, CDKN2A, Malignant Mesothelioma, Sarcomatoid, Carcinoma.

Related studies

• Utility of BAP1 Immunohistochemistry and p16 (CDKN2A) FISH in the Diagnosis of Malignant Mesothelioma in Effusion Cytology Specimens — H.C. Hwang, B.S. Sheffield, et al. (2016)
• Sarcomatoid Mesothelioma: A CDKN2A molecular analysis of 53 cases with immunohistochemical correlation with BAP1 — M. Zaleski, N. Kalhor, et al. (2020)
• BAP1 immunohistochemistry and p16 FISH results in combination provide higher confidence in malignant pleural mesothelioma diagnosis: ROC analysis of the two tests — T. Hida, M. Hamasaki, et al. (2016)
• 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)
• BAP1 immunohistochemistry has limited prognostic utility as a complement of CDKN2A (p16) fluorescence in situ hybridization in malignant pleural mesothelioma — S.M. McGregor, J. McElherne, et al. (2017)

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