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

作者：Howard B. Heidenberg, Isabell A. Sesterhenn, Jaya P. Gaddipati, Christopher M. Weghorst, Gregory S. Buzard, Judd W. Moul, Shiv K. Srivastava · 发表于：The Journal of Urology · 年份：1995 · DOI：10.1097/00005392-199508000-00024 · 被引用次数：160 · 研究领域：Cancer-related Molecular Pathways、Prostate Cancer Diagnosis and Treatment、Prostate Cancer Treatment and Research

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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%). CONCLUSIONS: Our study revealed a clear progression of increased p53 alteration from untreated primary to hormone refractory disease (p < 0.00005).