Increased E2F-1 expression via tumour cell proliferation and decreased apoptosis are correlated with adverse prognosis in patients with squamous cell carcinoma of the oesophagus.
BACKGROUND
The retinoblastoma (Rb) pathway, which governs cell cycle progression, is frequently genetically altered in cancer, causing deregulated expression of the E2F-1 transcription factor, which promotes DNA synthesis and cell cycle progression. Recent studies show that E2F-1 also participates in apoptosis induction in a p53 dependent or independent manner. Despite its crucial role and paradoxical effects on cell turnover, the function of E2F-1 in human cancer is unclear.


OBJECTIVE
To evaluate E2F-1 expression using immunohistochemistry in 43 surgically resected oesophageal squamous cell carcinoma (OSCC) specimens.


METHODS
This study analysed the association of E2F-1 with tumour cell proliferation and apoptosis and the upstream regulators modulating these processes, and its impact on patient outcome. Tumour cell proliferation and apoptosis were assessed as percentage of MIB-1 positive or apoptotic cells (MIB-1 labelling index (MI) and apoptotic index (AI)), respectively.


RESULTS
Entire specimens showed abnormal expression of one or more upstream regulators of pRb/E2F-1. Although E2F-1 positivity was not associated with the expression of upstream regulators, it showed a linear and positive correlation with MI but not AI. Patients with high MI, low AI, or high E2F-1 positivity had significantly shorter recurrence free survival. By multivariate analysis, high MI and low AI were independently associated with recurrence free survival, but E2F-1 was not.


CONCLUSIONS
Increased cell proliferation and decreased apoptosis are associated with adverse prognosis in patients with OSCC. Although E2F-1 remains a controversial prognostic factor, its expression was closely associated with tumour cell proliferation and might influence clinical outcome, mainly via cell cycle progression.
Yamazaki
K
K
Department of Pathology, Teikyo University, Ichihara Hospital, Ichihara, 3426-3 Anesaki, Ichihara City, Chiba 299-0111, Japan. yamas@med.teikyo-u.ac.jp
Hasegawa
M
M
Ohoka
I
I
Hanami
K
K
Asoh
A
A
Nagao
T
T
Sugano
I
I
Ishida
Y
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D004812:Epidemiologic Methods; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D011379:Prognosis; D014157:Transcription Factors / Q000378:metabolism*
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D009363:Neoplasm Proteins; D014157:Transcription Factors