Hyperplastic polyps and serrated adenomas: precancerous lesions with mixed immunophenotype

Our immunohistochemical study wants to be a contribution to clarifying the adenoma-carcinoma sequence and serrated pathway of colorectal carcinogenesis. Thus, we performed immunohistochemical analysis of hyperplastic polyps (HP), serrated adenomas (SA), and classical adenomas (tubular adenomas - TA and tubulovillous adenomas - TVA) and carcinomas developed from adenomas (CA) using expression of p53, Ki-67, c-myc, APC, MSH2 and Ets-1 proteins. Because of correlation of the expression of these proteins, we propose several immunophenotypes, which show modifications along the known carcinogenetic mechanisms. Along the adenoma-carcinoma sequence we noted an increase in the expression of p53, Ki-67, c-myc and Ets-1, and a decrease in APC expression. The majority of TAs and TVAs are characterized by p53+÷Ki-67+, p53+÷c-myc+, p53+÷APC+, and Ets-÷p53+, Ets-÷Ki-67+ immunophenotypes. The majority of HPs and SAs are Ets-÷p53-, Ets-÷Ki-67+, Ets-÷c-myc+, APC+÷MSH2-. In approximately 1÷3 of the hyperplastic polyps and serrated adenomas, we noted that the decrease in expression of MSH2 is associated with an increase in the expression of p53, c-myc, Ki-67, and Ets-1. Thus, we can conclude that a group of hyperplastic polyps and serrated adenomas display similar immunohistochemical characteristics to tubular and tubulovillous adenomas, which delineates a group of precancerous lesions that can develop via mixed carcinogenic pathways.