P53 PROTEIN AND GENE ALTERATIONS IN PATHOLOGICAL STAGE-C PROSTATE CARCINOMA

Purpose: We determined the extent of p53 immunoreactivity in pathologi cal stage C prostate cancer as well as its correlation to tumor grade, substage, recurrence and proliferation rate. To define better the tem poral relationship of p53 nuclear reactivity in prostate cancer p53 im munoreactivity was evaluated in all associated prostatic intraepitheli al neoplasia lesions. Materials and Methods: Using immunohistochemistr y p53 status and proliferation rate were determined in 96 tumors from patients with pathological stage C prostate cancer. Single strand conf ormational polymorphism in exons 5 to 8 was used in a subset of specim ens to assess the association of p53 nuclear accumulation with mutatio ns in the p53 gene. Results: p53 Nuclear reactivity was demonstrated i n 10 tumors (10.4%), including 6 with high and 4 with low level nuclea r reactivity. Of the tumors 86 (89.6%) had no evidence of p53 immunore activity. Each of the 6 tumors with high level p53 reactivity had asso ciated areas of prostatic intraepithelial neoplasia that also showed p 53 nuclear reactivity. Furthermore, pathological stage C substage (C1, 2 or 3) was significantly associated with p53 nuclear reactivity(p = 0.04). Proliferation rates were correlated with p53 nuclear reactivity (p = 0.09), while there was no association with tumor grade or recurr ence. p53 Gene alterations were noted in 2 of the 3 p53 positive tumor s versus no alterations in the p53 gene of 3 p53 negative tumors. Conc lusions: p53 Nuclear accumulation is uncommon in pathological stage C prostate cancer and its presence in premalignant prostatic intraepithe lial neoplasia lesions suggests that it may be an early event in a sub set of prostate cancers.