Clinicopathologic evaluation of the trend toward histologically poor differentiation with submucosal invasion in superficial early colorectal adenocarcinomas

We examined differences in the degree of differentiation in intramucosal an d submucosal areas of involvement in early colorectal adenocarcinomas of 13 1 patients and compared these findings with tumor morphology. In addition, K-ras and p53 protein expression was determined in cases where poorly diffe rentiated adenocarcinoma was detected in the submucosa. We identified 6 pat ients with both intramucosal differentiated (well-to-moderately differentia ted) adenocarcinoma and submucosal poorly differentiated adenocarcinoma (Mw Sp). The morphological tumor type was superficial in all MwSp cases. The ob served MwSp adenocarcinomas had a significantly higher frequency of lymphat ic invasion than the more common superficial type of adenocarcinoma. Geneti c analysis of these MwSp lesions was carried out using the polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) method to det ect the presence of K-ras codon 12 point mutations, and an immunologic stai ning technique was used to identify the presence of p53 protein overexpress ion. The K-l-as mutation rate was 33.3%, and the p53 overexpression rate wa s 66.7% for the MwSp adenocarcinomas. Our findings suggest that the rapidly reduced histologic differentiation observed in some of these superficial c olorectal adenocarcinomas may play a role in their higher degree of invasiv eness.