Mutation of the transforming growth factor-β type II receptor gene in right-sided colorectal cancer: relationship to clinicopathological features and genetic alterations

• Published in: The Journal of pathology 1998-04, Vol.184 (4), p.390-395
• Main Authors: Iacopetta, Barry J., Welch, John, Soong, Richie, House, Anthony K., Zhou, Xiao-Ping, Hamelin, Richard
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Aged; Biological and medical sciences; coloractal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Female; Follow-Up Studies; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Male; Medical sciences; Microsatellite Repeats - genetics; Middle Aged; Mutation; Neoplasm Proteins - metabolism; p53; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Receptors, Transforming Growth Factor beta - genetics; replication error (RER); Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Survival Rate; transforming growth factor-β; Tumor Suppressor Protein p53 - metabolism; Tumors
• ISSN: 0022-3417; 1096-9896
• DOI: 10.1002/(SICI)1096-9896(199804)184:4<390::AID-PATH1230>3.0.CO;2-Q

The presence of inactivating mutations in the transforming growth factor‐β (TGF‐β) 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 various 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 showed 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. © 1998 John Wiley & Sons, Ltd.