Mutation of the transforming growth factor--beta type II receptor gene in right-sided colorectal cancer: Relationship to Clinicopathological features and genetic alterations

The presence of inactivating mutations in the transforming growth factor-beta (TGF-beta) type II receptor (RII) gene in colon cancer suggests that it may behave like a tumour suppressor gene. RII is mutated in the majority of colon tumours exhibiting widespread microsatellite instability, a characteristic generally referred to as the replication error phenotype (RER+). We investigated the association between RII mutations and vicious clinicopathological variables and genetic alterations in a large series of sporadic adenocarcinomas arising in the proximal colon. RII mutations were found in 17 per cent (36/210) of right-sided tumours and in 86 per cent (32/37) of those displaying RER+. They were associated with the absence of lymph node invasion (P=0.04), poor histological differentiation (P=0.006), and with a trend for improved patient survival. Tumours with an RII mutation also shelved non-significant trends for a lower incidence of p53 protein overexpression and of p53, K-ras, and APC gene mutation compared with tumours with normal RII. These results indicate that right-sided colorectal tumours containing RII mutations resemble those with the RER+ phenotype in terms of their clinicopathological features and genetic alterations. (C) 1998 John Wiley & Sons, Ltd.