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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

¹ Department of Pathology, Teikyo University, Ichihara Hospital, Ichihara, 3426-3 Anesaki, Ichihara City, Chiba, 299-0111, Japan
² Department of Pathology, Saitama Medical Centre, Saitama Medical School, Saitama, 350-8550 Japan
³ Department of Surgical Pathology, Tokyo Medical University, Shinjuku, Tokyo, 160-0023 Japan

Correspondence to:
Dr K Yamazaki
Department of Pathology, Teikyo University, Ichihara Hospital, 3426-3 Anesaki, Ichihara City, Chiba, 299-0111, Japan; yamas{at}med.teikyo-u.ac.jp 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.

Aims: 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.

Abbreviations: AI, apoptotic index; CDK, cyclin dependent kinase; HPV, human papillomavirus; LI, labelling index; MI, MIB-1 labelling index; OSCC, oesophageal squamous cell carcinoma; pRb retinoblastoma protein,

Keywords: oesophageal cancer; E2F-1; cell proliferation; apoptosis; squamous cell carcinoma

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