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

Klaus Jürgen Schmitz, Carmen Ina Müller, Henning Reis, Hakan Alakus, Günther Winde, Hideo Andreas Baba, Jeremias Wohlschlaeger, Bharat Jasani, Joachim Fandrey, Kurt Werner Schmid

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1287-1296
Number of pages10
JournalInternational Journal of Colorectal Disease
Volume24
Issue number11
DOIs
Publication statusPublished - Jun 16 2009

Keywords

  • Colorectal cancer
  • Hypoxia-inducible factor
  • Metallothionein
  • Prognosis

ASJC Scopus subject areas

  • Gastroenterology

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