Aberrant Pax-8 expression in well-differentiated papillary mesothelioma and malignant mesothelioma of the peritoneum: a clinicopathologic study

Our plain-English summary of Aberrant Pax-8 expression in well-differentiated papillary mesothelioma and malignant mesothelioma of the peritoneum: a clinicopathologic study, by D. Xing, N. Banet, R. Sharma, et al (Human Pathology, 2018).

The study

• Authors: D. Xing, N. Banet, R. Sharma, R. Vang, B.M. Ronnett, P.B. Illei
• Journal: Human Pathology
• Published: 2018;72:160-166
• Cited by: 33 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Serous ovarian neoplasms can overlap morphologically with peritoneal mesothelial proliferations, including well-differentiated papillary mesothelioma (WDPM) and malignant epithelioid mesothelioma (MM). Accurate histologic classification of these neoplasms is important for clinical management. The Pax-8 protein is commonly used for differentiating peritoneal MM from serous carcinoma, but the diagnostic value of Pax-8 for distinguishing WDPM from borderline or low-grade serous tumors is unknown. We used immunohistochemistry staining to assess Pax-8 expression in 33 WDPMs, 34 peritoneal MMs, 48 pleural MMs, 11 adenomatoid tumors, 5 peritoneal inclusion cysts, and 51 benign/reactive mesothelium specimens. Staining was noted in 20 WDPMs (61%), with 17 showing strong and diffuse nuclear staining and 3 patchy/focal staining. Calretinin was expressed in 33 cases (100%), whereas focal BerEP4 staining was noted in 2 of 29 cases (7%). In contrast, 4 peritoneal MM (12%) were Pax-8 positive (3 diffuse and 1 focal staining). All adenomatoid tumors and peritoneal inclusion cysts were negative for Pax-8. Of the 48 pleural MM cases, 2 (4%) showed focal weak to moderate nuclear labeling for Pax-8, and 2 cases (4%) of reactive mesothelium demonstrated focal and scattered Pax-8 staining. Pax-8 appears to be a useful marker for distinguishing MM from gynecologic malignancies but is not reliable for distinguishing WDPM from borderline or low-grade gynecologic lesions.

Copyright © 2017 Elsevier Inc. All rights reserved.

In plain English

This laboratory study from Johns Hopkins tested a tissue stain for the protein Pax-8. Pathologists use it to tell mesothelioma apart from ovarian-type serous tumors, and the authors asked whether it works the same way in well-differentiated papillary mesothelioma (WDPM) of the peritoneum. They examined 33 peritoneal WDPMs and 34 peritoneal malignant mesotheliomas from hospital and consultation files. They also examined 48 pleural malignant mesotheliomas, 11 adenomatoid tumors, 5 peritoneal inclusion cysts and 51 benign or reactive mesothelium samples. The article did not study asbestos or any other exposure. Pax-8 staining was found in 20 of 33 WDPMs (61%), compared with 4 of 34 peritoneal malignant mesotheliomas (12%), 2 of 48 pleural malignant mesotheliomas (4%) and 2 of 51 benign or reactive mesothelium samples (4%). All adenomatoid tumors and inclusion cysts were negative. The authors concluded that Pax-8 is useful for separating malignant mesothelioma from gynecologic cancers but not reliable for separating WDPM from borderline or low-grade gynecologic lesions. They named their use of a polyclonal antibody and limited follow-up data as limitations.

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 clinicopathologic and immunohistochemistry (tissue staining) study of archived pathology cases
• Who was studied: Archived cases from the files of the Johns Hopkins Hospital: 33 peritoneal WDPMs (31 female and 2 male patients, aged 8 to 77) and 34 peritoneal malignant mesotheliomas (27 female and 7 male patients, aged 30 to 82). Of these 67 tumors, 15 were in-house cases and 52 were consultations. The study also included 11 adenomatoid tumors, 5 peritoneal inclusion cysts, 51 benign/reactive mesothelium specimens, and 48 pleural malignant mesotheliomas on tissue microarrays. Study dates were not given.
• Main results:
  • Pax-8 nuclear staining was found in 20 of 33 WDPMs (61%). In 17 cases the staining was strong to moderate and diffuse, and in 3 it was patchy or focal.
  • All 6 WDPMs with invasive foci stained for Pax-8: 5 diffusely and 1 focally.
  • The 3 WDPMs that occurred together with serous tumors (atypical proliferative serous tumor, invasive low-grade serous carcinoma or high-grade serous carcinoma) were all Pax-8 negative. The authors said the significance of this is unknown.
  • All 33 WDPMs stained for calretinin. Of 29 WDPMs tested for BerEP4 or MOC31, 27 were negative and 2 showed focal staining.
  • In peritoneal malignant mesothelioma, 4 of 34 cases (12%) were Pax-8 positive: 3 diffuse and 1 focal.
  • All 11 adenomatoid tumors and all 5 peritoneal inclusion cysts were Pax-8 negative.
  • In pleural malignant mesothelioma, 2 of 48 cases (4%) showed focal weak to moderate Pax-8 staining. In benign/reactive mesothelium, 2 of 51 cases (4%) showed focal or scattered staining.
  • Follow-up data were available for 14 WDPM patients, and 12 were alive with no evidence of disease after 0.5 to 93 months. The Pax-8 staining pattern did not appear to correlate with clinical outcome.
• The authors' conclusion: The authors concluded that Pax-8 is a useful marker for distinguishing malignant mesothelioma from gynecologic malignancies. They found it not reliable for distinguishing WDPM and other benign or borderline mesothelial lesions from superficial epithelial proliferations of the gynecologic tract. They stated that Pax-8 should be used together with calretinin and an epithelial marker such as BerEP4 or MOC31.
• Limitations the authors state:
  • The authors used a polyclonal Pax-8 antibody, which raises concern about non-specific staining.
  • Follow-up data were limited because most cases were seen in consultation.
  • The authors said a larger number of cases is needed to understand the significance of Pax-8 expression in peritoneal mesothelioma.

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: Well-Differentiated Papillary Mesothelioma, Malignant Mesothelioma, Peritoneum, Neoplasm, Epithelioid, Mesothelioma, Carcinoma, Immunohistochemistry.

Related studies

• Well-differentiated papillary mesothelioma of the female peritoneum: a clinicopathologic study of 26 cases — A. Malpica, S. Sant'Ambrogio, et al. (2012)
• Well-differentiated papillary mesothelioma of the peritoneum: a diagnostic dilemma on fine-needle aspiration cytology — J.G. Nasit, G. Dhruva (2014)
• Incidental finding of multiple well-differentiated papillary mesotheliomas in peritoneum — M. Jakobsen, B. Engvad, et al. (2016)
• First somatic mutation of E2F1 in a critical DNA binding residue discovered in well-differentiated papillary mesothelioma of the peritoneum — W. Yu, W. Chan-On, et al. (2011)
• Therapeutic strategies for well-differentiated papillary mesothelioma of the peritoneum — Y.K. Lee, H.J. Jun, et al. (2013)
• Well-differentiated papillary mesothelioma: A 17-year single institution experience with a series of 75 cases — M. Sun, L. Zhao, et al. (2019)

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