Previous studies have shown that nuclear p53 over-expression is an indicato
r 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 adenocarc
inomas. The purpose was to examine whether mutations occur in cases with p5
3 accumulated in the cytoplasm and whether there are any differences in the
frequency and characteristics of p53 mutations in different staining patte
rns. In the present study, we identified P53 mutations using PCR single-str
and conformation polymorphism (SSCP) and DNA sequencing in 75 primary color
ectal 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 simila
r to those with nuclear p53 expression. However, the tumors with accumulati
on in both the nucleus and cytoplasm demonstrated a higher mutation rate. W
e suppose that the role of cytoplasmic p53 accumulation in predicting progn
osis in patients with colorectal cancer may be dependent on both mutational
and non-mutational mechanisms. (C) 2001 Wiley-Liss, Inc.