PAX8 reliably distinguishes ovarian serous tumors from malignant mesothelioma

Our plain-English summary of PAX8 reliably distinguishes ovarian serous tumors from malignant mesothelioma, by A.R. Laury, J.L. Hornick, R. Perets, et al (The American Journal of Surgical Pathology, 2010).

The study

• Authors: A.R. Laury, J.L. Hornick, R. Perets, J.F. Krane, J. Corson, R. Drapkin, M.S. Hirsch
• Journal: The American Journal of Surgical Pathology
• Published: 2010;34(5):627-35
• Cited by: 168 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Ovarian serous neoplasms can have morphologic overlap with malignant mesothelioma. The distinction is clinically important, yet most studies have failed to identify immunostains that reliably distinguish these 2 tumor types. Recently, transcription factor PAX8 was shown to be a sensitive and relatively specific marker for Müllerian tumors. In addition, some studies suggest that h-caldesmon is sensitive and specific for mesothelioma when compared with serous ovarian tumors. The goal of this study was to evaluate whether PAX8 and h-caldesmon expression can successfully distinguish mesothelioma from serous ovarian tumors. Immunohistochemistry was carried out using PAX8 and h-caldesmon antibodies on archival tissue from 254 ovarian serous tumors and 50 mesothelial tumors. Nuclear and cytoplasmic immunoreactivity were considered positive for PAX8 and h-caldesmon, respectively. PAX8 staining was present in 99% of high-grade serous ovarian carcinomas and all (100%) low-grade ovarian carcinomas and serous borderline tumors; however, only 74% of these cases (188/254) were diffusely positive in more than 50% of tumors cells, and intensity ranged from strong to weak. None of the pleural malignant mesotheliomas were reactive with PAX8. However, 2/23 (9%) peritoneal malignant mesotheliomas showed focal and/or weak staining for PAX8; the remaining cases were negative. Two well-differentiated papillary mesotheliomas and 1 multicystic mesothelioma each showed some staining for PAX8. h-caldesmon was negative in all serous neoplasms and all mesothelial neoplasms, except 1 pleural malignant mesothelioma which showed patchy immunoreactivity. Strong PAX8 staining is highly specific (P<0.00001) for ovarian serous tumors when compared with malignant mesotheliomas of the peritoneum and pleura. The presence of weak staining for PAX8 in the 3 "noninvasive" mesotheliomas questions the use for PAX8 in this differential diagnosis. On the basis of this study, h-caldesmon is not a useful marker for mesothelioma.

In plain English

This laboratory study from Boston's Brigham and Women's Hospital tested whether two tissue stains could help pathologists tell ovarian serous tumors from mesothelioma, which can look alike. It did not study asbestos exposure. The authors stained archived tissue from 304 cases collected between 1998 and 2009: 254 ovarian serous tumors and 50 mesothelial tumors. The PAX8 stain was positive in 253 of 254 ovarian serous tumors (99.6%), though only 188 of 254 stained in more than half of tumor cells. All 24 pleural malignant mesotheliomas were negative for PAX8. Two of 23 peritoneal malignant mesotheliomas showed weak staining in scattered areas. Both well-differentiated papillary mesotheliomas and the one multiloculated cystic mesothelioma also stained. Comparing ovarian serous tumors with malignant mesothelial tumors, the authors reported a sensitivity of 99.6% and a specificity of 95.7%. The second stain, h-caldesmon, was negative in all tumors except one pleural malignant mesothelioma. The authors concluded that PAX8 is highly sensitive and specific for ovarian serous tumors compared with malignant or invasive mesothelial tumors. They noted that staining in the three noninvasive mesotheliomas questions its use for this diagnosis.

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: Diagnostic immunohistochemistry study of archived tissue samples (laboratory pathology study)
• Who was studied: 304 archived cases from 1998 to 2009 at Brigham and Women's Hospital, Boston: 50 mesothelial tumors (23 peritoneal malignant epithelioid mesotheliomas, 2 peritoneal well-differentiated papillary mesotheliomas, 1 peritoneal multiloculated inclusion cyst or 'multicystic mesothelioma', 24 pleural malignant epithelioid mesotheliomas), 102 low-grade ovarian serous tumors (92 serous borderline tumors, 10 low-grade serous carcinomas) and 152 high-grade serous ovarian carcinomas
• Exposure: No asbestos or other exposure was studied. The tissues were stained with two markers: PAX8 (assessed for nuclear staining) and h-caldesmon (assessed for cytoplasmic staining)
• Main results:
  • PAX8 was positive in 253 of 254 (99.6%) ovarian serous tumors (151/152 high-grade serous carcinomas and all 102 low-grade serous tumors)
  • Only 188 of 254 ovarian serous tumors stained diffusely, in more than 50% of tumor cells, and staining intensity ranged from strong to weak
  • All 24 pleural malignant mesotheliomas were negative for PAX8
  • 2 of 23 peritoneal malignant mesotheliomas showed multifocal weak PAX8 staining; the other 21 were negative
  • Both peritoneal well-differentiated papillary mesotheliomas showed weak PAX8 staining, and the one multiloculated cystic mesothelioma was PAX8 positive
  • When ovarian serous tumors were compared with malignant mesothelial tumors (not all 50 mesothelial tumors), PAX8 had a sensitivity of 99.6% and a specificity of 95.7% (P<0.00001)
  • h-caldesmon was negative in all tumors except 1 of 24 pleural malignant mesotheliomas, which showed patchy staining
  • A subset of 17 peritoneal mesothelial tumors was also stained with h-caldesmon at the more concentrated 1:100 dilution, and all remained negative
• The authors' conclusion: The authors concluded that PAX8 is highly sensitive and specific for ovarian serous tumors when compared with malignant or invasive mesothelial tumors, and that it may be most helpful with small pleural or peritoneal biopsies. They also concluded that, on the basis of this study, h-caldesmon is not a useful marker for mesothelioma.
• Limitations the authors state:
  • Weak PAX8 staining in the 3 noninvasive mesotheliomas (2 well-differentiated papillary, 1 multicystic) questions the use of PAX8 for this diagnosis
  • The one PAX8-negative high-grade serous carcinoma was tested on a tissue microarray, and its negative result may be a false negative from sampling error

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Neoplasm, Mesothelioma, Immunohistochemistry, Carcinoma, Well-Differentiated Papillary Mesothelioma, Multicystic Mesothelioma (MCM), Peritoneum.

Related studies

• Value of PAX8, PAX2, claudin-4, and h-caldesmon immunostaining in distinguishing peritoneal epithelioid mesotheliomas from serous carcinomas — N.G. Ordóñez (2013)
• PAX8 Expression in a Subset of Malignant Peritoneal Mesotheliomas and Benign Mesothelium has Diagnostic Implications in the Differential Diagnosis of Ovarian Serous Carcinoma — D.B. Chapel, A.N. Husain, et al. (2017)
• Expression of the Ets transcription factor EHF in serous ovarian carcinoma effusions is a marker of poor survival — K. Brenne, D.A. Nymoen, et al. (2012)
• 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)
• 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)
• Is PAX2 a reliable marker in differentiating diffuse malignant mesotheliomas of peritoneum from serous carcinomas of müllerian origin? — F.F. Gao, A.M. Krasinskas, et al. (2012)

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