PAX8 Expression in a Subset of Malignant Peritoneal Mesotheliomas and Benign Mesothelium has Diagnostic Implications in the Differential Diagnosis of Ovarian Serous Carcinoma

Our plain-English summary of PAX8 Expression in a Subset of Malignant Peritoneal Mesotheliomas and Benign Mesothelium has Diagnostic Implications in the Differential Diagnosis of Ovarian Serous Carcinoma, by D.B. Chapel, A.N. Husain, T. Krausz, et al (The American Journal of Surgical Pathology, 2017).

The study

• Authors: D.B. Chapel, A.N. Husain, T. Krausz, S.M. McGregor
• Journal: The American Journal of Surgical Pathology
• Published: 2017;41(12):1675-1682
• Type of article: Case report
• Cited by: 54 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Distinguishing malignant peritoneal mesothelioma (MPM) from serous carcinoma involving the peritoneum remains a diagnostic challenge, particularly in small biopsy and cytology specimens. In this distinction, PAX8 expression has been regarded as a specific marker of serous carcinoma. In addition, BAP1 loss is reportedly specific to MPM, in the distinction from both benign mesothelial lesions and ovarian serous tumors (OSTs). Using immunohistochemistry, we examined PAX8 and BAP1 expression in 27 MPMs, 25 cases of benign mesothelium, and 45 OSTs. Five MPMs were PAX8 (5/27, 18%), while 8 cases of benign mesothelium expressed PAX8 (8/25, 32%). PAX8 expression in mesothelium was significantly more common in women than in men (P=0.01). Sixteen MPMs exhibited BAP1 loss (16/25, 64%), while BAP1 was retained in all benign mesothelium and all OSTs. All cases of PAX8 mesothelium were negative for expression of estrogen receptor. These data show that PAX8 is expressed in both benign and malignant mesothelium, and that BAP1 loss is highly specific for MPM, in the differential with both benign mesothelial proliferations and OTSs. These results also have implications for primary diagnosis and for pathologic staging of OST. Caution should be applied when PAX8 expression is used to distinguish mesothelial and serous proliferations, and BAP1 loss may be confirmatory in cases where mesothelioma is favored.

In plain English

This study used tissue staining to check two markers, PAX8 and BAP1, in all malignant peritoneal mesotheliomas diagnosed at the University of Chicago between January 2003 and June 2016. There were 27 cases, in 14 women and 13 men. For comparison, the authors stained 25 benign mesothelial samples and a group of ovarian serous tumors. PAX8 has been treated as a marker of ovarian serous tumors. It was found in 5 of 27 (18%) peritoneal mesotheliomas, 3 with diffuse staining, and in 8 of 25 (32%) benign mesothelial samples. PAX8 in mesothelium was significantly more common in women than in men (P=0.01). BAP1 was lost in 17 of 27 (63%) mesotheliomas but kept in all benign samples and all ovarian serous tumors. All PAX8-positive mesothelial lesions were negative for estrogen receptor. The authors concluded that PAX8 is not entirely specific for müllerian (ovarian-type) lesions and urged extreme caution when a diagnosis rests mainly on PAX8. They noted that the study had only a small number of PAX8-positive cases from a single institution. The study did not look at 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 single-institution pathology study using immunohistochemistry (tissue staining) on mesothelioma cases, with benign mesothelial lesions and ovarian serous tumors as comparison groups
• Who was studied: 27 malignant peritoneal mesotheliomas (14 women, 13 men, all epithelioid) diagnosed at the University of Chicago, January 2003 to June 2016. Comparison groups: 25 benign mesothelial samples (10 well-differentiated papillary mesotheliomas, 4 benign multicystic mesotheliomas, 11 reactive mesothelium) and ovarian serous tumors (high-grade and low-grade serous carcinomas and serous borderline tumors)
• Exposure: No asbestos or other environmental exposure was studied. The study examined staining for PAX8, BAP1 and estrogen receptor in tissue samples.
• Main results:
  • PAX8 was present in 5 of 27 (18%) malignant peritoneal mesotheliomas (polyclonal antibody): 3 (11%) diffuse and 2 (7%) focal
  • PAX8 was present in 8 of 25 (32%) benign mesothelial samples
  • PAX8 expression in mesothelium was significantly more common in women than in men (P=0.01)
  • All PAX8-positive benign mesothelial lesions, and all 3 mesotheliomas with diffuse PAX8, occurred in women
  • How often PAX8 appeared in benign mesothelial lesions was not significantly different from mesothelioma (P=0.34)
  • BAP1 was retained in all 25 benign mesothelial samples and lost in 17 of 27 (63%) mesotheliomas (P < 0.001)
  • All ovarian serous tumors examined showed diffuse PAX8, and all retained BAP1
  • All PAX8-positive mesothelial lesions, benign and malignant, were negative for estrogen receptor
  • BAP1 loss was not significantly more frequent in PAX8-positive than in PAX8-negative mesotheliomas (P = 0.12)
  • Results with a second (monoclonal) PAX8 antibody were nearly identical
• The authors' conclusion: The authors concluded that PAX8 is not entirely specific for müllerian lesions when the alternative is a peritoneal mesothelial lesion, and that extreme caution is needed when an ovarian serous tumor diagnosis rests mainly on PAX8 positivity
• Limitations the authors state:
  • Only a small number of PAX8-positive mesotheliomas were studied
  • The cases came from a single institution
  • Some PAX8-positive mesotheliomas may have been misdiagnosed as ovarian tumors, biasing retrospective studies against finding them

Topics

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

Medical terms in this study, explained in our Lexicon: Peritoneal Mesothelioma, Mesothelium, Differential Diagnosis, Ovarian Serous Carcinoma, Carcinoma, Peritoneum, Biopsy, Cytology.

Related studies

• The diagnostic and molecular characteristics of malignant mesothelioma and ovarian/peritoneal serous carcinoma — B. Davidson (2011)
• Cytokeratin 5/6 expression, prognosis, and association with estrogen receptor α in high-grade serous ovarian carcinoma — E.T. Taube, C. Denkert, et al. (2017)
• CD24 is highly useful in differentiating high-grade serous carcinoma from benign and malignant mesothelial cells — B. Davidson (2016)
• Loss of BAP1 expression is very rare in peritoneal and gynecologic serous adenocarcinomas and can be useful in the differential diagnosis with abdominal mesothelioma — J. Andrici, J. Jung, et al. (2016)
• 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)
• Nongynecologic metastases to fallopian tube mucosa: a potential mimic of tubal high-grade serous carcinoma and benign tubal mucinous metaplasia or nonmucinous hyperplasia — J.T. Rabban, P. Vohra, et al. (2015)

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