We examined histological findings, p53 overexpressions 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 immunohistochemical 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 depressed-type or polypoid-type sm cancers. Among 60 sm cancer samples, depressed-type sm cancers were found in 9 (15%) and polypoid-type sm cancers were found in 51 (85%). The frequency of p53 expression was significantly higher in depressed-type [7/9 (78%)] as compared to polypoid-type [18/51 (35%)] sm cancers (p<0.05). The frequency of K-ras codon 12 point mutations was significantly lower in depressed-type [0/9 (0%)] as compared to polypoid-type [23/51 (45%)] sm cancers (p<0.05). We conclude that the development of depressed-type cancers may involve a distinct genetic pathway.

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