Does early polypoid colorectal cancer with depression have a pathway other than adenoma-carcinoma sequence?

In the carcinogenesis of colorectal cancer, the concept of adenoma-carcinoma sequence is widely accepted. In this pathway, polypoid adenoma develops into early polypoid cancer and then progresses to advanced cancer. Alternatively, some groups insist that in the de novo pathway in which early cancers develop without preexisting adenoma, flat or depressed early cancers develop into advanced cancer. According to these two different concepts of carcinogenesis, early polypoid cancers may include two distinct types of lesions, early polypoid cancers without central depression via the adenoma-carcinoma sequence and early polypoid cancers with central depression via de novo carcinogenesis. We analyzed 45 submucosal cancer specimens histologically diagnosed as polypoid by clinicopathological features and K-ras mutation in early polypoid cancers with and without depression to clarify whether there was a difference between the two groups. No significant difference in clinicopathological features was found between the two groups. Also, a high incidence of K-ras mutation was observed in both groups. This suggests that early polypoid cancers with depression have a similar genetic background to polypoid cancers without depression, which follows the adenoma-carcinoma sequence. It is possible that whether or not the tumor has a depression does not indicate the distinct pathway of colorectal carcinogenesis.