p53 Overexpression and K-ras Codon 12 Mutations in Submucosal Invasive Colorectal Cancer

We examined histological findings, p53 overexpression and K-ras codon 12 mutations and the histology of submucosal invasive (sm) colorectal cancers. Sixty specimens of sporadic sm cancer were obtained by surgical resection or endoscopic polypectomy. p53 expression was examined by im-munohistochemical staining using the streptavidin-biotin method. K-ras codon 12 mutations were detected by polymerase chain reaction (PCR) and dot blot hybridization. These tumors were classified as horizontal or nonhorizontal growth sm cancers. Fifteen of 60 (25%) superficial type horizontal growth cancers gave rise to sm cancers. There was no significant difference in size between horizontal and nonhorizontal growth sm cancers. There was no significant difference in the frequency of p53 expression between horizontal [8/15 (53.3%)] and nonhorizontal [22/45 (48.9%)] growth sm cancers. The frequency of K-ras codon 12 point mutations was significantly lower in horizontal growth [0/15 (0%)] sm cancers as compared to nonhorizontal growth [22/45 (48.9%)] sm cancers. We conclude that the development of superficial type horizontal growth cancers may involve a distinct genetic pathway.