The relationship between E2F family members and tumor growth in colorectal adenocarcinomas: A comparative immunohistochemical study of 100 cases.
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.
*Laboratory of Histology and Embryology, School of Medicine, National and Kapodistrian University of Athens, Athens †Laboratory of Anatomy, School of Medicine, Democritus University of Thrace, Alexandroupolis ‡Department of Surgery, Didimotichon General Hospital, Didimotichon, Greece.
Athanasios
A
Xanthoulis
Athanassios
A
Kotsinas
Dina
D
Tiniakos
Aliki
A
Fiska
Antonios-Apostolos
AA
Tentes
Aspasia
A
Kyroudi
Christos
C
Kittas
Vassilios
V
Gorgoulis
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology; D050687:E2F1 Transcription Factor / Q000378:metabolism*; D050703:E2F2 Transcription Factor / Q000378:metabolism*; D050704:E2F4 Transcription Factor / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D012189:Retrospective Studies
D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D050703:E2F2 Transcription Factor; C493761:E2F2 protein, human; D050704:E2F4 Transcription Factor; C493762:E2F4 protein, human; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins