Flat-elevated and depressed, subtypes of flat early colorectal cancers, should be distinguished by their pathological features.

Flat-type colorectal tumors have are being detected with increasing frequency. It has become clear that these flat lesions contain two subtypes; flat-elevated and depressed lesions. However, their clinicopathological features and roles in colorectal carcinogenesis remain obscure. We classified colorectal adenomas and submucosal invasive cancers into three types: polypoid, flat-elevated, and depressed types. A clinicopathological study of 2505 colorectal tumors (2407 adenomas, 98 submucosal invasive cancers) was then performed. Furthermore, 64 tumors (25 adenomas with high-grade dysplasia, 39 submucosal invasive cancers) from which DNA was extracted were examined for K-ras gene mutation. The percentages of each configuration in the resected materials were 62.0%, 36.4%, and 1.6% of the polypoid, flat-elevated, and depressed types, respectively. The rate of submucosal invasive cancer in the depressed type was always high regardless of size. In the polypoid and flat-elevated types, lesions of larger size showed higher rates of invasion. Analysis of submucosal invasive cancers revealed no adenomatous components in any of the depressed-type lesions; in the polypoid and flat-elevated types the frequencies of cancer with adenomatous components were 83.6% and 77.8%, respectively. The flat-elevated type was more frequently located (77.8%) in the proximal colon than the other types (polypoid type 16.4%, depressed type 25.0%). The incidence of K-ras gene mutation was 47.2%, 18.2%, and 0% in the polypoid, flat-elevated, and depressed types, respectively. These findings suggest that the flat-elevated and depressed types are similar in that they are both morphologically flat and have infrequent incidences of K-ras gene mutation, but these two lesions differ in their pathological features. Especially, depressed type lesions have a tendency to invade the submucosal layer even when they are small. Therefore one should always be aware of this type of lesion during colonoscopic examination.