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

Abstract:

We examined differences in the degree of differentiation in intramucosal and submucosal areas of involvement in early colorectal adenocarcinomas of 131 patients and compared these findings with tumor morphology. In addition, K-ras and p53 protein expression was determined in cases where poorly differentiated adenocarcinoma was detected in the submucosa. We identified 6 patients with both intramucosal differentiated (well-to-moderately differentiated) adenocarcinoma and submucosal poorly differentiated adenocarcinoma (MwSp). The morphological tumor type was superficial in all MwSp cases. The observed MwSp adenocarcinomas had a significantly higher frequency of lymphatic invasion than the more common superficial type of adenocarcinoma. Genetic analysis of these MwSp lesions was carried out using the polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) method to detect the presence of K-ras codon 12 point mutations, and an immunologic staining technique was used to identify the presence of p53 protein overexpression. The K-ras mutation rate was 33.3%, and the p53 overexpression rate was 66.7% for the MwSp adenocarcinomas. Our findings suggest that the rapidly reduced histologic differentiation observed in some of these superficial colorectal adenocarcinomas may play a role in their higher degree of invasiveness.