Immunohistochemical phenotype of malignant mesothelioma: predictive value of CA125 and HBME‐1 expression

Abstract

Histological diagnosis of malignant mesothelioma and differentiation from adenocarcinoma is often difficult. Definitive pathological confirmation of malignant mesothelioma requires demonstration of an appropriate immunohistochemical phenotype. Selection of an optimum panel of immunohistochemical antibodies for the reliable identification of malignant mesothelioma is hindered by the absence of a specific immunohistochemical label for mesothelioma cells. Recently, we have found that the ovarian carcinoma cell antibody CA125 labels malignant mesothelioma cells, and the antibody HBME-1 has been developed as a sensitive mesothelial cell marker. We have compared the immunohistochemical staining patterns achieved with CA125 and HBME-1 to those obtained using a panel of eight further antibodies in 17 malignant mesotheliomas and 14 primary and secondary adenocarcinomas within lung and pleura. CA125 labelled malignant mesothelioma cells in 15 of 17 cases (88%), and adenocarcinoma cells in seven of 14 cases (50%). HBME-1 labelled mesothelioma cells in all 17 cases (100%) but also labelled adenocarcinoma cells in 10 of 14 cases (71%). BerEP4 positively labelled one malignant mesothelioma but was negative in the remaining 16 cases and positively labelled nine of 14 adenocarcinomas (64%). Monoclonal anti-CEA, AUA-1, CA19.9 and LeuM1 labelled no malignant mesotheliomas and were positive in 10 (71%), nine (64%), eight (57%) and six (43%) of 14 cases of adenocarcinoma, respectively. Diastase-PAS staining detected neutral mucin in none of the malignant mesotheliomas but in 10 (71%) of the 14 adenocarcinomas. We conclude that CA125 and HBME-1 do not label mesothelial cells with sufficient specificity to be useful for differentiating malignant mesothelioma from adenocarcinoma, although negative staining with HBME-1 makes a diagnosis of malignant mesothelioma unlikely. As there remains an absence of a specific positive mesothelial cell marker this distinction is still most reliably made using a panel of antibodies including at least two of the following: anti-CEA, AUA-1, BerEP4, LeuM1 and CA19.9, in combination with histochemical assessment of neutral mucin production.

Ber-EP4 and Anti-Calretinin Antibodies: A Useful Combination for Differential Diagnosis of Various Histological Types of Ovarian Cancer Cells and Mesothelial Cells

“…Our findings were consistent with those previous reports. Results from our study described the immuno-reactive expression of immunoreactivity of epithelial related antigens, cytokeratin 18, EMA and CA125 in the great majority of ovarian carcinomas and mesothelial tissues, a finding consistent with previous reports (Delahaye et al 1991(Delahaye et al , 1997Bateman et al 1997;Ordoñez 1998a;Attanoos et al 2002). These results suggest that these markers are not necessarily helpful in distinguishing adenocarcinomas of the ovary from a reactive and/or neoplastic mesothelium.…”

Recognition of Mesothelin by the Therapeutic Antibody MORAb-009

“…Although the physiological function of mesothelin is unclear, studies have shown that it is capable of binding to the tumor antigen CA-125 (also known as MUC16) and mediates cell adhesion (10 -12). CA-125 is a well documented biomarker for ovarian cancers (13), and the majority (88%) of mesothelioma cases are also CA-125-positive on the cell membrane (14), suggesting the possibility that binding of tumor-associated CA-125 to mesothelin on normal mesothelial cells lining the pleura or peritoneum can lead to heterotypic cell adhesion and tumor metastasis within the pleural and peritoneal cavities. By truncation and alanine replacement mutagenesis, the CA-125 binding site was mapped to a 64-residue fragment at the N terminus of mesothelin (12).…”

Diagnostic value of MUC4 immunostaining in distinguishing epithelial mesothelioma and lung adenocarcinoma

“…4,[8][9][10][11] Although it seems that LeuM1 (anti-CD15) may be specific, it is less sensitive than the other antibodies. 12,13 Results on CEA sensitivity and specificity are very controversial in the literature due to the use of various monoclonal or polyclonal antibodies. In the largest series, CEA immunostaining is positive in about 90% of adenocarcinomas and weakly and focally positive in 10% of mesotheliomas.…”