E2F-1 overexpression correlates with decreased proliferation and better prognosis in adenocarcinomas of Barrett oesophagus.
BACKGROUND
E2F-1 expression is positively associated with tumour growth in oesophageal squamous-cell carcinomas (OSCC), while it exhibits oncosuppressive features in colonic adenocarcinomas (AC). To date there are no data regarding E2F-1 expression and its relationship with tumour kinetics (proliferation, apoptosis) in adenocarcinomas that develop on Barrett oesophagus.


OBJECTIVE
As oesophageal adenocarcinomas occur almost exclusively in the metaplastic Barrett epithelium and the opposing E2F-1 behaviour seems to be cell and tissue-type dependent, we examined the manner in which E2F-1 acts in ACs of Barrett oesophagus.


METHODS
We estimated the immunohistochemical expression of E2F-1, Ki-67, caspase-3 and p53 immunohistochemical status in 35 Barrett oesophagus ACs.


RESULTS
E2F-1 immunopositivity correlated inversely with Ki-67, by semi-serial section and statistical analysis (p = 0.023, Spearman correlation). Semi-serial section analysis revealed a direct association between E2F-1 and caspase-3 staining. No correlation was found with p53 status. Cases with higher E2F-1 immunoexpression exhibited longer survival (p = 0.047, Cox-regression).


CONCLUSIONS
E2F-1 expression was negatively related to tumour proliferation in ACs of Barrett oesophagus. Additionally, E2F-1 immunohistochemical status correlated positively with patient survival. These findings are opposite from those seen in OSCCs, suggesting that the tumour-suppressing E2F-1 behaviour in oesophageal adenocarcinomas is possibly due to the intestinal-type nature of the metaplastic Barrett mucosa.
Evangelou
K
K
Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, University of Athens, Greece.
Kotsinas
A
A
Mariolis-Sapsakos
T
T
Giannopoulos
A
A
Tsantoulis
P K
PK
Constantinides
C
C
Troupis
T G
TG
Salmas
M
M
Kyroudis
A
A
Kittas
C
C
Gorgoulis
V G
VG
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D001471:Barrett Esophagus / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D049109:Cell Proliferation; D050687:E2F1 Transcription Factor / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D009367:Neoplasm Staging; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D009363:Neoplasm Proteins