Immunohistochemical Determination of P53 Protein Nuclear Accumulation in Prostatic Adenocarcinoma

Abstract

Abnormalities of the TP53 gene are currently the most common genetic alterations associated with human malignancy. The study of altered patterns of p53 protein expression in primary prostate cancer has to date yielded a much lower incidence of alteration compared to bladder, colon, lung and breast cancer. However, the analysis of prostate cancer metastases 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) and an immunohistochemical method in 93 paraffin embedded tumors (48 primary tumors, 29 lymph node metastases and 16 bone metastases) to assess p53 nuclear accumulation. Overall, p53 nuclear accumulation was observed in 19 tumors (20%), including 17 with PAb 1801 and CM-1 immunoreactivities, and 2 with CM-1 immunoreactivity only. The pattern of p53 immunoreactivity was heterogeneous in most tumors, with only 3 cases exhibiting homogeneous staining. Primary, lymph node and bone metastases exhibited p53 nuclear staining in 9 of 48 (19%), 2 of 29 (7%) and 8 of 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 immunoreactivity was expressed (p = 0.002). P53 nuclear accumulation was significantly more common in higher grade primary tumors (p = 0.007). Our results suggest that p53 nuclear accumulation is relatively uncommon in prostate cancer. However, p53 nuclear accumulation appears to be associated with advanced stages of disease, as illustrated by its relatively higher occurrence in hormone refractory tumors and bone metastases. Furthermore, the significantly greater prevalence of p53 accumulation in bone metastases is currently the highest reported for prostate cancer.