[Show abstract][Hide abstract] ABSTRACT: The mammalian E2F family of transcription factors comprises a group of 8 proteins, which either activate or repress transcription of numerous target genes, playing a role in cell-cycle progression and apoptosis. We have collectively investigated the immunohistochemical expression of E2F1, E2F2, and E2F4 transcription factors and their relation to cell kinetic parameters using serial section analysis in a series of 100 cases of human colorectal adenocarcinomas. E2F1 and E2F4 expressed nuclear immunopositivity in all cases. The range of their expression was 2% to 80% (mean 21%±15%) and 2% to 90% (mean 66%±20%), respectively. E2F2 was expressed in 41 cases at low levels (range, 1% to 5%, mean 2%±9%). A statistically significant direct association between E2F4 and cell proliferation, as expressed by high levels of Ki-67 labeling index, was shown. A mutually exclusive immunostaining pattern between E2F1 and E2F4 and a direct correlation of E2F1 and apoptosis were also highlighted. Our results point to a possible direct tumor-promoting role for E2F4 in the context of colorectal carcinogenesis. The inverse immunohistochemical relationship between E2F1 and E2F4 indicates a possible mechanistic interlink in colorectal cancer. Low expression of E2F2 may reflect functional redundancy between members of the E2F family, in this case between E2F1 and E2F2.
Applied immunohistochemistry & molecular morphology: AIMM / official publication of the Society for Applied Immunohistochemistry 06/2012; DOI:10.1097/PAI.0b013e3182598198 · 2.06 Impact Factor