Molecular genetics and diagnosis of renal cell tumors

Abstract

Renal cell tumors display notoriously an intra- and intertumoral morphological heterogeneity making a reproducible cytomorphological diagnosis impossible. To overcome the cytological heterogeneity, the "Heidelberg Classification of Renal Cell Tumours" is soundly based on the genetic lesions that underlie the formation of distinct tumors. Allelic loss of chromosome 3 p and mutation of the VHL gene specify conventional renal cell carcinoma. In addition duplication of chromosome 5 q as well as allelic losses of prognostic value at chromosomes 6 q, 8 p, 9 p and 14 q characterize conventional renal cell carcinomas. Papillary renal cell tumors, which display an adenoma-carcinoma sequence, are marked by trisomies of chromosomes 3 q, 7, 8 p, 12 q, 16 q, 17 q und 20 as well as loss of the Y chromosome in males. Chromophobe renal cell carcinoma shows a low chromosome number due to monosomy of chromosomes 1, 2, 6, 10, 13, 17, and 21. Benign tumors, such as renal oncocytoma and metanephric adenoma, can also be diagnosed by genetic means. The distinct types of tumors have different biological behaviour and therefore, an accurate classification is considered clinically important. We worked out a quick and reproducible fluorescent microsatellite assay for detecting allelic changes. This technique is useful for postoperative and retrospective diagnosis as well as for preoperative analysis of fine needle aspiration specimens.