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Combined analysis of hypoxia-inducible factor 1 alpha and metallothionein indicates an aggressive subtype of colorectal carcinoma

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Purpose

Hypoxia-inducible factor 1 (HIF-1) is a hypoxia-induced transcription factor that regulates gene expression in critical pathways involved in tumour growth and metastasis. Metallothionein (MT) is a group of small molecular weight cysteine-rich proteins with a broad variety of functions. The present study aimed to analyse the prognostic impact of HIF-1α and MT expression in colorectal cancer and to evaluate a possible link of combined HIF-1α and MT expression with colorectal cancer progression.

Materials and methods

We investigated the relationship of HIF-1α and MT with each other and clinicopathological parameters including proliferative activity (Ki67) and apoptosis (terminal desoxyribonucleotide transferase-mediated dUTP nick-end labelling) using immunohistochemistry.

Results

HIF-1α expression was identified as an independent prognostic parameter in multivariate survival analysis and characterised an aggressive cancer phenotype. In addition, HIF-1α was significantly linked to an increased expression of MT.

Conclusions

HIF-1α expression qualified as an independent prognostic and characterised an aggressive cancer phenotype associated with an increased expression of MT. Our study suggests that MT can be added to the complex biological pathways induced by hypoxia in human cancer tissue.

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Conflicts of interest

All authors declare no financial and personal relationships with other people or organisations that could inappropriately influence (bias) their work.

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Authors and Affiliations

  1. Institute of Pathology and Neuropathology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45122, Essen, Germany

    Klaus Jürgen Schmitz, Henning Reis, Hideo Andreas Baba, Jeremias Wohlschlaeger & Kurt Werner Schmid

  2. Institute of Physiologie, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

    Carmen Ina Müller & Joachim Fandrey

  3. Department of Visceral and Vascular Surgery, University of Cologne, Cologne, Germany

    Hakan Alakus

  4. Department of Gastrointestinal Surgery, Klinikum Herford, Herford, Germany

    Günther Winde

  5. Department of Pathology, University of Wales College of Medicine, Cardiff, UK

    Bharat Jasani

Authors
  1. Klaus Jürgen Schmitz
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  2. Carmen Ina Müller
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  3. Henning Reis
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  4. Hakan Alakus
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  6. Hideo Andreas Baba
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  7. Jeremias Wohlschlaeger
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  8. Bharat Jasani
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  9. Joachim Fandrey
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  10. Kurt Werner Schmid
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Corresponding author

Correspondence to Klaus Jürgen Schmitz.

Additional information

Klaus Jürgen Schmitz and Carmen Ina Müller contributed equally to this study.

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Schmitz, K.J., Müller, C.I., Reis, H. et al. Combined analysis of hypoxia-inducible factor 1 alpha and metallothionein indicates an aggressive subtype of colorectal carcinoma. Int J Colorectal Dis 24, 1287–1296 (2009). https://doi.org/10.1007/s00384-009-0753-8

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  • DOI: https://doi.org/10.1007/s00384-009-0753-8

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