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Increasing expression of hypoxia-inducible proteins in the Barrett's metaplasia–dysplasia–adenocarcinoma sequence

Hypoxia-associated markers are involved in the progression of several malignancies, but are relatively unstudied in Barrett's carcinogenesis. Our aim was to assess the immunohistochemical expression of hypoxia-inducible factor (HIF)-1α, HIF-2α, erythropoietin (Epo), Epo receptor (Epo-R), Glut-1...

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Detalles Bibliográficos
Autores principales: Griffiths, E A, Pritchard, S A, McGrath, S M, Valentine, H R, Price, P M, Welch, I M, West, C M L
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360174/
https://www.ncbi.nlm.nih.gov/pubmed/17437013
http://dx.doi.org/10.1038/sj.bjc.6603744
Descripción
Sumario:Hypoxia-associated markers are involved in the progression of several malignancies, but are relatively unstudied in Barrett's carcinogenesis. Our aim was to assess the immunohistochemical expression of hypoxia-inducible factor (HIF)-1α, HIF-2α, erythropoietin (Epo), Epo receptor (Epo-R), Glut-1 and vascular endothelial growth factor (VEGF) along with Ki67/MIB-1 in the Barrett's metaplasia–dysplasia–adenocarcinoma sequence. Endoscopic biopsies of normal squamous epithelium (NSE) (n=20), columnar-lined oesophagus (CLO) (n=15), CLO with intestinal metaplasia (n=20), dysplasia (n=17) and Barrett's type adenocarcinoma (n=20) were obtained. Immunohistochemistry was performed on the paraffin-embedded tissue. A score was calculated for each marker (range 0−300) by multiplying intensity (none 0, weak 1, moderate 2, strong 3) by percentage of expression (range 0–100). Significant increases in the expression of HIF-2α (P=0.014), VEGF (P<0.0001), Epo-R (P<0.0001) and Ki67 (P<0.0001) were found as tissue progressed from NSE to adenocarcinoma. HIF-2α was expressed late in the sequence and was only seen in dysplasia and adenocarcinoma. High HIF-2α expression was seen in 12 out of 20 Barrett's type adenocarcinoma. The late expression of HIF-2α in the Barrett's carcinogenesis sequence and its high expression in adenocarcinoma suggest that it is worth further investigation as a marker of disease progression and therapeutic target.