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

• Published in: Journal of clinical pathology Vol. 58; no. 9; pp. 904 - 910
• Main Authors: Yamazaki, K, Hasegawa, M, Ohoka, I, Hanami, K, Asoh, A, Nagao, T, Sugano, I, Ishida, Y
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and Association of Clinical Pathologists 01-09-2005; BMJ; BMJ Publishing Group LTD; Copyright 2005 Journal of Clinical Pathology
• Subjects: Adult; Aged; Aged, 80 and over; Apoptosis; apoptotic index; Biological and medical sciences; Biomarkers, Tumor - metabolism; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; CDK; Cell Cycle Proteins - metabolism; Cell Proliferation; cyclin dependent kinase; DNA-Binding Proteins - metabolism; E2F Transcription Factors; E2F-1; E2F1 Transcription Factor; Epidemiologic Methods; Esophageal Neoplasms - metabolism; Esophageal Neoplasms - pathology; Female; Genes; HPV; Human papillomavirus; Humans; Investigative techniques, diagnostic techniques (general aspects); Kinases; labelling index; Male; Medical sciences; MIB-1 labelling index; Middle Aged; Neoplasm Proteins - metabolism; oesophageal cancer; oesophageal squamous cell carcinoma; Original; OSCC; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; pRb retinoblastoma protein; Prognosis; squamous cell carcinoma; Studies; Transcription Factors - metabolism; Human; Cell proliferation; Anatomic pathology; Squamous cell carcinoma; Prognosis; Digestive system; Cell death; Transcription factor E2F1; Malignant tumor; Tumor cell; Apoptosis; Esophagus
• ISSN: 0021-9746; 1472-4146
• DOI: 10.1136/jcp.2004.023127

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.