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Hypoxia, angiogenesis and apoptosis markers in locally advanced rectal cancer

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Background and aims

Hypoxia-inducible factor 1α (HIF-1α) is a critical regulatory protein of cellular response to hypoxia. HIF-1α triggers the angiogenic process through activation of the vascular endothelial factor (VEGF) gene. The bcl-2 anti-apoptotic and the death promoting p53 genes, regulate the apoptotic cell death. We investigated the relationship between hypoxia, angiogenesis and apoptosis and their prognostic impact in patients with advanced rectal cancer.

Patients and methods

The immunohistochemical expression of HIF-1α, VEGF, p53 and bcl-2 and the determination of microvessel density (MVD), apoptotic index (AI) were carried out in tumour tissue samples obtained from 92 patients with locally advanced rectal cancer (LARC) (T3,4/N±).

Results

HIF-1α high reactivity and VEGF overexpression were noted in 47.8 and 44.6% of the examined cases, respectively. They significantly correlated with lymph node metastasis (P<0.001) and low rectal location (P=0.016). HIF-1α expression was directly correlated with VEGF up-regulation (P<0.001) and MVD (P<0.001). VEGF expression was closely interrelated with MVD (P<0.001). In univariate analysis advanced grade, infiltrative pattern of tumour growth, vascular invasion, positive lymph node status, HIF-1α expression and VEGF upregulation were related to decreased disease-free and overall survival. In multivariate analysis, only high HIF-1α reactivity and positive lymph node status emerged as independent variables of adverse prognostic significance.

Conclusion

HIF-1α and VEGF may play an important predictive and prognostic role in patients with LARC.

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Author information

Authors and Affiliations

  1. 1st Propaideutic Surgical Department, Hippocration University Hospital, Athens, Greece

    George E. Theodoropoulos, John Bramis & Dimitrios Panoussopoulos

  2. Department of Pathology, School of Medicine, University of Athens, Athens, Greece

    Andreas C. Lazaris, Vasilios E. Theodoropoulos, Kalliopi Papatheodosiou & Efstratios Patsouris

  3. Department of Biology, School of Medicine, University of Athens, Athens, Greece

    Maria Gazouli

  4. 41 Chrysippou Street, 15773, Zografou, Athens, Greece

    George E. Theodoropoulos

Authors
  1. George E. Theodoropoulos
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Correspondence to George E. Theodoropoulos.

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Theodoropoulos, G.E., Lazaris, A.C., Theodoropoulos, V.E. et al. Hypoxia, angiogenesis and apoptosis markers in locally advanced rectal cancer. Int J Colorectal Dis 21, 248–257 (2006). https://doi.org/10.1007/s00384-005-0788-4

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