Clear Cell Papillary Renal Cell Carcinoma and RenalAngiomyoadenomatous Tumor – Two Variants of a MorphologicImmunohistochemical and Genetic Distinct Entity of Renal CellCarcinoma

摘要

Clear cell papillary renal cell carcinoma (ccpRCC) and renal angiomyoadenomatous tumor (RAT) share morphologic similarities with clear cell (ccRCC) and papillary renal cell carcinoma (pRCC). It is a matter of controversy whether their morphologic, immunophenotypic and molecular features allow the definition of a separate renal carcinoma entity. The aim of our project was to investigate specific renal immunohistochemical biomarkers involved in the hypoxia-inducible factor pathway and mutations in the VHL gene to clarify the relationship between ccpRCC and RAT. We investigated 28 ccpRCC and 9 RAT samples by immunohistochemistry using 25 markers. VHL gene mutations and allele losses were investigated by Sanger sequencing and fluorescence in situ hybridization (FISH). Clinical follow-up data were obtained for a subset of the patients. No tumor recurrence or tumor-related death was observed in any of the patients. Immunohistochemistry and molecular analyses led to the reclassification of three tumors as ccRCC and TFE3 translocation carcinomas. The immunohistochemical profile of ccpRCC and RAT samples was very similar but not identical, differing from both ccRCC and pRCC. Especially, the parafibromin and hKIM-1 expression exhibited differences in ccpRCC/RAT comparedwith ccRCC and pRCC. Genetic analysis revealed VHL mutations in 2/27(7%) and 1/7 (14%) ccpRCC and RAT samples, respectively. FISHanalysis disclosed a 3p loss in 2/20 (10 %) ccpRCC samples. ccpRCC andRAT have a specific morphologic and immunohistochemical profile but they sharesimilarities with the more aggressive renal tumors. Based on our results, weregard ccpRCC/RAT as a distinct entity of renal cell carcinomas.