Vascular Expression of Prostate-specific Membrane Antigen (PSMA) in MiTF Family Translocation Renal Cell Carcinoma and Related Neoplasms

Abstract

Multiple studies have demonstrated prostate-specific membrane antigen (PSMA) expression in the neo-vasculature of non-prostate tumors including clear cell renal cell carcinoma (ccRCC). However, PSMA expression in rare renal tumors including MiTF family translocation renal cell carcinoma has not been previously characterized. We examined PSMA expression by immunohistochemistry in a series of MiTF family translocation renal cell carcinomas as well as in several genetically related tumors including alveolar soft part sarcoma and PEComas with TFE3 rearrangements. PSMA expression was also studied in several cases of ccRCC and papillary RCC. Overall, PSMA immunohistochemistry was performed in 61 samples from 58 patients. Vascular PSMA expression was seen with the highest frequency in ccRCC [88% (14/16)] (38% focal, 50% diffuse). Translocation RCC (tRCC) demonstrated the second highest frequency of PSMA expression [71% (22/28)] (57% focal, 14% diffuse), followed by alveolar soft part sarcoma [50% (4/8)] (38% focal, 12% diffuse). No PSMA expression was seen in PEComas with TFE3 rearrangement (0/3) or papillary RCC (0/6). PSMA expression was only present in tumor-associated neo-vasculature. A patient with oligometastatic tRCC underwent 68Ga-PSMA-11 PET imaging which detected multiple putative metastatic lesions not detected on conventional computed tomography imaging performed 2 weeks prior, supporting the potential utility of PSMA imaging in tRCC. These findings have potential implications for the utility of PSMA guided diagnostic and therapeutic agents in both common and uncommon renal cell carcinoma subtypes as well as genetically related mesenchymal neoplasms.