Cell Kinetics, p53 and bcl-2 Expression, and c-Ki-ras Mutations in Flat-Elevated Tubulovillous Adenomas and Adenocarcinomas of the Colorectum: Comparison with Polypoid Lesions

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Abstract
Background: Flat(-elevated) tubulovillous adenomas and adenocarcinomas of the colorectum constitute a specific type of neoplasm with superficial spreading growth. To establish their characteristics, a comparative investigation of a series of tumors was performed. Methods: A total of 56 flat tubulovillous tumors (39 adenomas, 17 invasive carcinomas) and 154 polypoid tubular or villous tumors (77 adenomas, 77 invasive carcinomas) were comparatively assessed for cell kinetics and molecular alterations. Results: Ki-67 labeling and p53 expression for both types of tumors increased along with degree of dysplasia or invasion, whereas bcl-2 expression showed an inverse decrease. However, apoptotic activity was invariably low in the flat tubulovillous tumors, as compared with the polypoid tumors, in which increase was apparent with tumor progression. The flat tubulovillous tumors also showed a higher frequency of c-Ki-ras mutations (92.9%) than the polypoid tubular tumors (40.0%). Conclusions: The flat tubulovillous tumor can be considered a distinct entity, with characteristics different from the polypoid counterpart.