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. Issue 9 (26th August 2005)

• Record Type: Journal Article
• Authors: Yamazaki, K; Hasegawa, M; Ohoka, I; Hanami, K; Asoh, A; Nagao, T; Sugano, I; Ishida, Y
• Is Part Of: Journal of clinical pathology. Volume 58:Issue 9(2005)
• Page Start: 904
• Page End: 910
• Publication Date: 2005-08-26
• Subjects: 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,; oesophageal cancer -- E2F-1 -- cell proliferation -- apoptosis -- squamous cell carcinoma; Pathology -- Periodicals; Pathology, Molecular -- Periodicals; 616.0705
• DOI: 10.1136/jcp.2004.023127
• Languages: English
• ISSNs: 0021-9746

Abstract

Abstract : 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.