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

• Published in: International journal of colorectal disease 2009-11, Vol.24 (11), p.1287-1296
• Main Authors: Schmitz, Klaus Jürgen, Müller, Carmen Ina, Reis, Henning, Alakus, Hakan, Winde, Günther, Baba, Hideo Andreas, Wohlschlaeger, Jeremias, Jasani, Bharat, Fandrey, Joachim, Schmid, Kurt Werner
• Format: Article
• Language: English
• Subjects: Amino Acids, Dicarboxylic - pharmacology; Apoptosis - drug effects; Biological and medical sciences; Cell Line, Tumor; Cell Proliferation - drug effects; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Epithelial Cells - pathology; Female; Gastroenterology; Gastroenterology. Liver. Pancreas. Abdomen; Hepatology; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Immunohistochemistry; Internal Medicine; Kaplan-Meier Estimate; Male; Medical sciences; Medicine; Medicine & Public Health; Metallothionein - metabolism; Original Article; Phenotype; Proctology; Reactive Oxygen Species - metabolism; Staining and Labeling; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Surgery; Tumors
• ISSN: 0179-1958; 1432-1262
• DOI: 10.1007/s00384-009-0753-8

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.