Early carcinogenic events in HNPCC adenomas: differences with sporadic adenomas

Tumorigenesis in hereditary nonpolyposis colorectal cancer (HNPCC) differs from that in sporadic colorectal cancer during the early stage. We examined the expression of proliferation- and apoptosis-regulating proteins in relation to proliferation and apoptosis in HNPCC and sporadic adenomas.

Proliferation and apoptosis were quantified, and the expression of cyclin B1, D3 and E, p21, p27, bcl-2, bax, p53 and cox-2 was determined by immunohistochemistry in 100 patients (42 with HNPCC and 48 with sporadic adenomas).

No differences between the two groups of patients in terms of proliferation and apoptosis were detected. Low-grade dysplastic HNPCC adenomas differed from sporadic ones by expressing bcl-2 more often (69 vs. 42%) and bax less often (50 vs. 73%). In comparison to sporadic adenomas, fewer high-grade dysplastic HNPCC expressed cyclin B1 and E (50 and 38% vs. 87 and 87%, respectively), p21 (6% vs. 53%) and bax (31% vs. 80%). In addition, HNPCC adenomas had a lower overexpression of p53 (5 vs. 19%).

The expression of cell cycle- and apoptosis-related proteins differs between HNPCC and sporadic adenomas from early through to advanced stages although proliferation and apoptosis are not different. These differences may contribute to the different clinical behavior of HNPCC and sporadic adenomas.