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

Autor: Griffiths EA; Academic Radiation Oncology, Division of Cancer Studies, Christie Hospital, The University of Manchester, Wilmslow Road, Withington, Manchester M20 4BX, UK., Pritchard SA, McGrath SM, Valentine HR, Price PM, Welch IM, West CM
Jazyk: angličtina
Zdroj: British journal of cancer [Br J Cancer] 2007 May 07; Vol. 96 (9), pp. 1377-83. Date of Electronic Publication: 2007 Apr 17.
DOI: 10.1038/sj.bjc.6603744
Abstrakt: 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)-1alpha, HIF-2alpha, 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-2alpha (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-2alpha was expressed late in the sequence and was only seen in dysplasia and adenocarcinoma. High HIF-2alpha expression was seen in 12 out of 20 Barrett's type adenocarcinoma. The late expression of HIF-2alpha 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.
Databáze: MEDLINE