Papillary renal carcinoma (PRC) comprises about 10% of all kidney epithelial tumors. Familiar/hereditary papillary renal carcinomas (HPRCs) have been described, but the majority of cases seem to be sporadic. HPRC is characterized by the predisposition to develop bilateral, multifocal renal tumors. Activating mutations in the tyrosine kinase domain (TK) of the hepatocyte growth factor (HGF) receptor, c-met, have been identified in both hereditary and sporadic PRC. The main aim of this study was to examine a family with no history of PRC in which the proband was a female patient affected by multiple and bilateral PRC at early onset. DNA mutation analysis has been performed by direct sequencing of exons 14-21 of c-met gene which include the TK domain. The proband displayed the germline c-met missense mutation g.3522G↷A in exon 16. Two other family members were found to carry the same mutation. The mutation analysis extended to 15 selected patients, allowed to identify the first case of an Italian patient affected by PRC displaying the somatic missense mutation g.3997 T↷C located in exon 19 of c-met. The mutation frequency of the selected-based population of PRC patients in this report was 12.5%. Furthermore, the phosphorylated c-met expression detected by immunohistochemistry in PRCs with germline/somatic or no c-met mutation, supports the concept that c-met activation may occur in PRC oncogenesis by c-met mutations and/or c-met over-expression.

•  Abstract
•  Download PDF