Alteration of the Tumor Suppressor Gene p53 in a High Fraction of Hormone Refractory Prostate Cancer

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Abstract
We studied the role of p53 tumor suppressor gene alteration in prostate cancer progression by demonstrating a difference in abnormal p53 findings between early and hormone refractory disease. The study included p53 immunohistochemistry of 26 archival transurethral resection specimens from patients with radiation recurrent and hormone refractory disease, 27 untreated primary tumors and 8 untreated metastatic lesions. p53 mutation analysis of tumor deoxyribonucleic acid (DNA) from microdissected specimens was done by cold single strand conformational polymorphism and DNA sequencing. Elevated p53 protein was present in 16 of 17 hormone refractory specimens (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%). Our study revealed a clear progression of increased p53 alteration from untreated primary to hormone refractory disease (p < 0.00005).