Fluorescence in situ hybridization for the detection of genetic alterations in prostate and bladder malignancies : Significance as a genetic marker to predict the patient prognosis

Sammanfattning: Prostate cancer and bladder cancer are common urological malignancies in man, while a lack of basic information underlying the oncogenesis and the tumor progression makes it difficult to form therapeutic strategies against these malignancies. Recent advances of molecular biology revealed that genetic alteration play a crucial role in the oncogenesis and progression of these tumors. Thus, deletions of chromosomes 8p (8p22 and 8p23-pter), lOq (lOq24-qter) and 16q (16q22-qter) were studied on 53 cases of prostate cancer. In 42 patients with transitional cell carcinoma (TCC), chromosomal deletion at 17p (pS3) were investigated. The numerical aberrations of chromosomes 7, 9, 10 and 11 were studied in 37 TCC cases. Forty-one (73%) cases with prostate cancer showed deletions of one or more regions of 8p. The results were confirmed by those of Southern blot study on 11 informative cases. A frequency of deletions of chromosome 8p (LPL and D8S7) were significantly increased in proportion to histopathological grade, while lOq (DlOS27) did not. As for chromosome 16q, the deletion of 16q (D16S155) was strongly associated with aberrant expression of E-cadherin, histopathological grade and tumor metastasis. A significantly higher frequency of progression was observed in patients with LPL deletion than those without deletion. A Cox-Hazard multivariate analysis revealed LPL deletion to be one of the significant prognostic factors as well as stage and D8S7, while neither DlOS27, nor D 16S 155 showed any correlation to disease progression. With regard to bladder cancer, 64% of specimens demonstrated p53 deletion with significant correlation with grade (pThese results suggest that i) non-random numerical aberrations might be early events of oncogenesis in bladder cancer, and ii) specific chromosomal aberrations, such as 8p in prostate cancer, or 17p deletion in bladder cancer, play a crucial role in the development of tumor progression, hence of clinical value as a diagnostic tool to predict the malignant potential and patient prognosis.