Molecular cytogenetic identification of cyclin D1 gene amplification in a renal pelvic tumor attributed to phenacetin abuse.

Despite extensive epidemiologic evidence of phenacetin abuse as a risk factor for renal pelvic carcinomas, genetic alterations in the resultant tumors remain largely unclear. In this report, a phenacetin-associated renal pelvic carcinoma (histologically a transitional-cell carcinoma) from an 80-year-old female patient was evaluated by molecular cytogenetic methods. Fluorescence in situ hybridization was used to identify chromosome gains or losses for the cyclin D1, p53, Rb and c-myc genes and the ploidy of their respective chromosomes. Cyclin D1 gene amplification, but normal copy numbers of p53, Rb and c-myc, and normal ploidy of chromosomes 8, 11, 13 and 17 were observed. Expression of cyclin D1 protein was confirmed by immunohistochemistry. In the absence of p53, Rb or c-myc abnormalities, the results suggested that cyclin D1 gene amplification and its protein overexpression may be involved in the genesis of renal pelvic carcinomas associated with phenacetin abuse.