Previous studies have shown that nuclear p53 over-expression is an indicator of p53 mutations whereas cytoplasmic p53 accumulation is related to wild-type p53 in several kinds of tumors. Cytoplasmic p53 accumulation has been demonstrated to be an independent prognostic factor in colorectal adenocarcinomas. The purpose was to examine whether mutations occur in cases with p53 accumulated in the cytoplasm and whether there are any differences in the frequency and characteristics of p53 mutations in different staining patterns. In the present study, we identified p53 mutations using PCR single-strand conformation polymorphism (SSCP) and DNA sequencing in 75 primary colorectal adenocarcinomas with different staining patterns (negative, nucleus, cytoplasm, nucleus and cytoplasm). The results show that the frequency and nature of mutations in tumors with cytoplasmic p53 accumulation were similar to those with nuclear p53 expression. However, the tumors with accumulation in both the nucleus and cytoplasm demonstrated a higher mutation rate. We suppose that the role of cytoplasmic p53 accumulation in predicting prognosis in patients with colorectal cancer may be dependent on both mutational and non-mutational mechanisms.
Copyright 2001 Wiley-Liss, Inc.