CLINICAL AND PATHOLOGICAL ASSOCIATIONS WITH P53 TUMOR-SUPPRESSOR GENE-MUTATIONS AND EXPRESSION OF P21(WAF1 CIP1) IN COLORECTAL-CARCINOMA/

Inactivation of the p53 tumour-suppressor gene is common in a wide var iety of human neoplasms. In the majority of cases, single point mutati ons in the protein-encoding sequence of p53 lead to positive immunohis tochemistry (IHC) for the p53 protein, and are accompanied by loss of the wild-type allele. Recently, the WAF1/Cip1 gene was identified as o ne of the genes induced by wild-type p53, and increased expression of p21(WAF1/Cip1) has been found to reflect the status of the p53 tumour- suppressor pathway. We investigated the inactivation of p53 in a relat ively small, but well-characterised, group of 46 colorectal carcinomas that were previously studied for allelic alterations, was oncogene mu tations and DNA aneuploidy. Alterations in p53 were identified by IHC, loss of 17p and DNA sequence analysis of exons 5-8, whereas p21(WAF1/ Cip1) protein expression was determined by IHC. p53 mutations were ide ntified in 19 of the 46 rumours (41%), whereas positive IHC for p53 wa s found in 21 of the 46 tumours (46%). Positive IHC for p21(WAF1/Cip1) was detected in 16 of 42 cases (38%). We found no relationship betwee n p21(WAF1/Cip1) staining and p53 protein expression or p53 mutational status. Inactivating mutations in the p53 gene correlated with LOH al 17p but not with LOH at 5q or 18q, Dukes' stage, tumour grade or DNA ploidy. There was a higher survival rate independent of Dukes' stage i n the group with no alterations in p53 compared with those with eviden ce of dysfunction of p53, bur the difference was not statistically sig nificant. We conclude that inactivation of p53 and altered expression of p21(WAF1/Cip1) are common in colorectal carcinoma but do not correl ate with each other or with the clinical or pathological parameters in vestigated.