P53 GENE-MUTATIONS, P53 PROTEIN ACCUMULATION AND COMPARTMENTALIZATIONIN COLORECTAL ADENOCARCINOMA

p53 accumulation may occur in the nucleus and/or cytoplasm of neoplast ic cells. Cytoplasmic accumulation has been reported to be an unfavora ble, but not established prognostic indicator in colorectal cancer. Di fferent types of p53 intracellular compartmentalization could depend e ither on p53 gene mutations or on the interaction with p53 protein lig ands. The purposes of our study were (1) to assess whether the differe nt patterns of p53 accumulation are selectively associated with p53 mu tations and (2) to evaluate the clinical significance of p53 mutations in colorectal carcinomas. We evaluated p53 gene mutations in exons 5 through 8, by polymerase chain reaction and single-strand conformation polymorphism analysis; p53 accumulation and intracellular compartment alization were detected immunocytochemically with the antibodies PAb18 01 and CM1. p53 mutations were found in 74 of 126 carcinomas (59%). Nu clear p53(PAb1801) (accumulation was associated with p53 gene mutation s (P < 0.001) whereas cytoplasmic p53 (CM1) accumulation was more like ly to occur with the wild-type p53 gene (P = 0.048). Overall, 112 carc inomas (89%) displayed p53 gene mutations and/or p53 accumulation of a ny type, p53 mutations were not correlated with important clinicopatho logical parameters and were not related to patient survival. Our data suggest that mechanisms other than mutations may also play a role in i nhibiting p53 tumor-suppressing functions in colorectal carcinomas. Cy toplasmic p53(CM1) accumulation frequently does not depend on p53 muta tions.