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J Clin Pathol 2005;58:904-910 doi:10.1136/jcp.2004.023127
  • Original article

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. K Yamazaki1,
  2. M Hasegawa1,
  3. I Ohoka1,
  4. K Hanami2,
  5. A Asoh1,
  6. T Nagao3,
  7. I Sugano1,
  8. Y Ishida1
  1. 1Department of Pathology, Teikyo University, Ichihara Hospital, Ichihara, 3426-3 Anesaki, Ichihara City, Chiba, 299-0111, Japan
  2. 2Department of Pathology, Saitama Medical Centre, Saitama Medical School, Saitama, 350-8550 Japan
  3. 3Department of Surgical Pathology, Tokyo Medical University, Shinjuku, Tokyo, 160-0023 Japan
  1. Correspondence to:
 Dr K Yamazaki
 Department of Pathology, Teikyo University, Ichihara Hospital, 3426-3 Anesaki, Ichihara City, Chiba, 299-0111, Japan; yamasmed.teikyo-u.ac.jp
  • Accepted 4 February 2005

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.

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