Anatomic Pathology / PRAME in Serosal Cancers

The PRAME (preferentially expressed antigen of melanoma) gene was previously shown to be overexpressed in ovarian/primary peritoneal serous carcinoma compared with malignant mesothelioma using gene expression arrays. The objective of this study was to validate this finding at the messenger RNA (mRNA) and protein levels. Quantitative real-time polymerase chain reaction analysis of 126 müllerian carcinomas and 23 malignant mesotheliomas showed significantly higher PRAME mRNA expression in the former tumor (P < .001; test sensitivity and specificity, 89% and 91%, respectively). PRAME protein was expressed in 41 of 50 müllerian carcinomas and 0 of 30 mesotheliomas usin g Western blotting (P < .001; test sensitivity and specificity, 82% and 100%, respectively). PRAME levels in müllerian carcinoma were unrelated to survival; however, PRAME protein expression was up-regulated in solid metastases compared with primary carcinoma and effusions (P < .001). Our data confirm that PRAME effectively differentiates müllerian carcinoma from malignant mesothelioma at the mRNA and protein levels, suggesting a role in the diagnostic workup of serosal cancers. The serosal cavities, including the peritoneal, pleural, and pericardial spaces, are frequently affected by cancer. The presence of cancer cells in effusions at these anatomic sites is evidence of advanced-stage disease with metastatic spread and, regardless of the tumor site of origin, marks disease progression and is generally associated with poor survival.1 One of the most challenging differential diagnoses at this anatomic site is between müllerian serous carcinoma and malignant mesothelioma (MM), tumors that are closely related in terms of clinical manifestations, morphologic features, and immunohistochemical phenotype.2 We recently reported on the differential expression of 189 genes in ovarian/primary peritoneal serous carcinoma and diffuse malignant peritoneal mesothelioma (DMPM) effusions studied by using complementary DNA microarray technology.3 Among the differentially expressed genes, PRAME was identified as a gene that is significantly overexpressed in ovarian/primary peritoneal serous carcinoma effusions compared with DMPM. Preferentially expressed antigen of melanoma (PRAME) is a 509-amino-acid protein originally identified as an antigen recognized by cytotoxic T lymphocytes from a patient with melanoma.4-6 The tumor antigen PRAME is a nonmutated gene whose expression is mostly restricted to tumor cells, as most normal tissues do not express PRAME, the exceptions being testis and, to an even lesser extent, the endometrium, ovary, and adrenal gland. In addition, miniscule amounts of PRAME were found in some samples originating from the kidney, brain, and skin.4 The function of PRAME was unknown before the discovery of its acting as repressor of retinoic acid receptor signaling. Upon completion of this activity you will be able to: • define the biological role of PRAME (preferentially expressed antigen of melanoma). • describe the distribution of PRAME in normal tissue and cancer. • describe the diagnostic and clinical role of PRAME. The ASCP is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The ASCP designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit TM per article. Physicians should claim only the credit commensurate with the extent of their participation in the activity. This activity qualifies as an American Board of Pathology Maintenance of Certification Part II Self-Assessment Module. The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose. Questions appear on p 317. Exam is located at www.ascp.org/ajcpcme.