IMMUNOHISTOCHEMICAL DETERMINATION OF P53 PROTEIN NUCLEAR ACCUMULATIONIN PROSTATIC ADENOCARCINOMA

Abnormalities of the TP53 gene are currently the most common genetic a lterations associated with human malignancy. The study of altered patt erns of p53 protein expression in primary prostate cancer has to date yielded a much lower incidence of alteration compared to bladder, colo n, lung and breast cancer. However, the analysis of prostate cancer me tastases has been limited. The objective of our study was to determine the prevalence of p53 nuclear accumulation in primary, metastatic and hormone refractory prostatic adenocarcinoma, and to characterize its relationship with conventional clinicopathological variables. We used 2 antibodies (mouse monoclonal PAb 1801 and rabbit polyclonal CM-1) an d an immunohistochemical method in 93 paraffin embedded tumors (48 pri mary tumors, 29 lymph node metastases and 16 bone metastases) to asses s p53 nuclear accumulation. Overall, p53 nuclear accumulation was obse rved in 19 tumors (20%), including 17 with PAb 1801 and CM-1 immunorea ctivities, and 2 with CM-1 immunoreactivity only. The pattern of p53 i mmunoreactivity was heterogeneous in most tumors, with only 3 cases ex hibiting homogeneous staining. Primary, lymph node and bone metastases exhibited p53 nuclear staining in 9 of 48 (19%), 2 of 29 (7%) and 8 o f 16 (50%) cases, respectively (p = 0.003). In 6 of 10 primary hormone refractory tumors (60%) and in 3 of 38 primary hormone naive tumors ( 8%) p53 nuclear immunereactivity was expressed (p = 0.002). P53 nuclea r accumulation was significantly more common in higher grade primary t umors (p = 0.007). Our results suggest that p53 nuclear accumulation i s relatively uncommon in prostate cancer. However, p53 nuclear accumul ation appears to be associated with advanced stages of disease, as ill ustrated by its relatively higher occurrence in hormone refractory tum ors and bone metastases. Furthermore, the significantly greater preval ence of p53 accumulation in bone metastases is currently the highest r eported for prostate cancer.