Combined analysis of hypoxia-inducible factor 1 alpha and metallothionein indicates an aggressive subtype of colorectal carcinoma.
OBJECTIVE
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-1alpha and MT expression in colorectal cancer and to evaluate a possible link of combined HIF-1alpha and MT expression with colorectal cancer progression.


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


CONCLUSIONS
HIF-1alpha 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.
Schmitz
Klaus Jürgen
KJ
Institute of Pathology and Neuropathology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45122 Essen, Germany. klaus.schmitz@uni-duisburg-essen.de
Müller
Carmen Ina
CI
Reis
Henning
H
Alakus
Hakan
H
Winde
Günther
G
Baba
Hideo Andreas
HA
Wohlschlaeger
Jeremias
J
Jasani
Bharat
B
Fandrey
Joachim
J
Schmid
Kurt Werner
KW
D000600:Amino Acids, Dicarboxylic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008668:Metallothionein / Q000378:metabolism*; D010641:Phenotype; D017382:Reactive Oxygen Species / Q000378:metabolism; D013194:Staining and Labeling
D000600:Amino Acids, Dicarboxylic; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017382:Reactive Oxygen Species; D008668:Metallothionein; C040947:oxalylglycine