Monoclonal antibody to a proximal nephrogenic renal antigen: immunohistochemical analysis of formalin-fixed, paraffin-embedded human renal cell carcinomas.

An IgG1 murine monoclonal antibody (PN-15) to an epitope preserved in formalin-fixed, paraffin-embedded tissue sections of renal cell carcinomas was developed following immunization of mice with the microsomal fraction of human renal cortical tissue homogenates. An immunohistochemical screening procedure was utilized against fixed, embedded tissue sections of renal cell carcinomas. This antibody identified a Mr 200,000 determinant on immuno-Western blot analysis, and the recognized epitope was shown to reside in the carbohydrate domain of a Mr 200,000 glycoprotein (gp200). Analysis of its tissue distribution was performed by indirect immunoperoxidase staining of fixed, embedded tissue sections of the following: 36 different types of normal tissues; 45 primary and 38 metastatic renal cell carcinomas; and 124 cases of 39 different types of neoplasms. In the normal kidney, gp200 was localized along the brush border of the proximal tubule and the luminal surface of Bowman's capsule adjoining the outgoing proximal tubule. Shared tissue localization was also noted in breast lobules and ducts, parathyroid gland, and epididymis. The gp200 was expressed by 93% of primary and 84% of metastatic renal cell carcinomas, primarily on the cell surface membrane. Shared antigenic expression was noted in relatively few other tumors including: mammary carcinomas; teratocarcinomas; and parathyroid adenomas. The PN-15 monoclonal antibody holds promise as a useful reagent in retrospective investigations of fixed, embedded cases of renal cell carcinomas. The antibody may also be of practical utility in diagnostic immunohistochemistry by helping to retrospectively define the primary site of metastatic clear cell tumors, especially when fresh frozen tissue from such tumors is not available.