Value of PAX8, PAX2, claudin-4, and h-caldesmon immunostaining in distinguishing peritoneal epithelioid mesotheliomas from serous carcinomas

Abstract

Distinguishing between peritoneal epithelioid mesotheliomas and papillary serous carcinomas involving the peritoneum can be difficult on routine histological preparations, but this differential diagnosis can be facilitated by the use of immunohistochemistry. Recent investigations have indicated that PAX8, PAX2, claudin-4, and h-caldesmon are immunohistochemical markers that can assist in distinguishing between these two malignancies; however, much of the information published on the value of these markers is either insufficient or contradictory. The purpose of this study is to resolve some of the existing controversies and to fully determine the practical value of these markers for assisting in the differential diagnosis between peritoneal mesotheliomas and serous carcinomas. In order to do so, a total of 40 peritoneal epithelioid mesotheliomas and 45 serous carcinomas (15 primary, 30 metastatic to the peritoneum) were investigated. PAX8 and PAX2 nuclear positivity was demonstrated in 42 (93%) and 25 (56%) of the serous carcinomas, respectively, whereas none of the mesotheliomas expressed either marker. Forty-four (98%) of the serous carcinomas exhibited claudin-4 reactivity along the cell membrane, whereas none of the mesotheliomas were positive for this marker. All of the serous carcinomas and mesotheliomas were negative for h-caldesmon. Based on these results, it is concluded that PAX8 and claudin-4 have a higher sensitivity and specificity for assisting in discriminating between peritoneal epithelioid mesotheliomas and serous carcinomas when compared with all of the other positive carcinoma markers that are, at present, recommended to be included in the immunohistochemical panels used in this differential diagnosis. Even though it is highly specific, PAX2 has little practical value in the diagnosis of peritoneal epithelioid mesotheliomas as its sensitivity is low. The h-caldesmon is not useful.

Diagnostic Usefulness of Claudin-3 and Claudin-4 for Immunocytochemical Differentiation between Metastatic Adenocarcinoma Cells and Reactive Mesothelial Cells in Effusion Cell Blocks

“…Claudin-3 and claudin-4 are major structural molecules of the tight junctions that link epithelial cells. Because these two claudins are frequently observed in a variety of carcinomas of different origins, but rarely detectable in mesothelial cells, several studies confirmed that claudin-3 and claudin-4 are highly specific and sensitive immunohistochemical markers for distinguishing primary or metastatic carcinomas from neoplastic or reactive mesothelium [18,19,20,21]. …”

“…These included various epithelial markers such as carcinoembryonic antigen (CEA), Ber-Ep4, E-cadherin, MOC-31, and mucins [6,8,19,21,27,28]. However, immunocytochemical staining for these epithelial markers was unable to detect cases with MAC that did not express them.…”

“…Several studies demonstrated that immunohistochemical analysis of claudin-3 and claudin-4 expression can be used to differentiate metastatic adenocarcinomas from neoplastic or reactive mesothelium [18,19,20,21]. In this study, we evaluated the diagnostic usefulness of claudin-3 and claudin-4 to distinguish MAC from RMC in cell blocks prepared from effusion specimens.…”

“…Differential expression of various members of the claudin family in cancer can be used to confirm the histological identity of certain cancers, while excluding others. Because both claudin-3 and claudin-4 are frequently expressed in many types of adenocarcinomas of various origins, but are rarely detectable in mesothelial cells, immunohistochemical analysis of claudin-3 and claudin-4 expression can be used to differentiate metastatic adenocarcinomas from neoplastic or reactive mesothelium [18,19,20,21]. …”

The Utility of Immunohistochemistry in the Differential Diagnosis of Gynecologic Disorders

“…Nearly all carcinomas were positive for PAX8 and membranous claudin-4, whereas none of the mesotheliomas exhibited reactivity with these markers. 135,136 Moreover, vascular endothelial growth factor receptor 2 (VEGFR2) was identified as a supplemental marker to identify malignant mesothelioma with promising results. Strong expression of VEGFR was demonstrated in malignant epithelioid mesothelioma but rarely in other epithelial tumors.…”