ALTERATION OF THE TUMOR-SUPPRESSOR GENE P53 IN A HIGH FRACTION OF HORMONE-REFRACTORY PROSTATE-CANCER

Purpose: We studied the role of p53 tumor suppressor gene alteration i n prostate cancer progression by demonstrating a difference in abnorma l p53 findings between early and hormone refractory disease. Materials and Methods: The study included p53 immunohistochemistry of 26 archiv al transurethral resection specimens from patients with radiation recu rrent and hormone refractory disease, 27 untreated primary tumors and 8 untreated metastatic lesions. p53 mutation analysis of tumor deoxyri bonucleic acid (DNA) from microdissected specimens was done by cold si ngle strand conformational polymorphism and DNA sequencing. Results: E levated p53 protein was present in 16 of 17 hormone refractory specime ns (94%), 4 of 8 untreated metastatic tumors (50%) and 6 of 27 primary untreated tumors (22%). DNA analysis of representative specimens with elevated p53 confirmed p53 gene alterations in 9 of 11 cases (82%). C onclusions: Our study revealed a clear progression of increased p53 al teration from untreated primary to hormone refractory disease (p<0.000 05).