Metabolic markers in relation to hypoxia; staining patterns and colocalization of pimonidazole, HIF-1α, CAIX, LDH-5, GLUT-1, MCT1 and MCT4

BMC Cancer

Research Article

Jasper Lok¹  Saskia E Rademakers¹  Albert J van der Kogel¹  Johan Bussink¹  Johannes HAM Kaanders¹ 

[1] Department of Radiation Oncology, 874 Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500, Nijmegen, HB, The Netherlands;

关键词: Metabolic Marker;    Node Positive Patient;    Hypoxic Area;    Cervical Squamous Cell Carcinoma;    CAIX Expression;   

DOI  :  10.1186/1471-2407-11-167

 received in 2010-11-19, accepted in 2011-05-12,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundThe cellular response of malignant tumors to hypoxia is diverse. Several important endogenous metabolic markers are upregulated under hypoxic conditions. We examined the staining patterns and co-expression of HIF-1α, CAIX, LDH-5, GLUT-1, MCT1 and MCT4 with the exogenous hypoxic cell marker pimonidazole and the association of marker expression with clinicopathological characteristics.Methods20 biopsies of advanced head and neck carcinomas were immunohistochemically stained and analyzed. All patients were given the hypoxia marker pimonidazole intravenously 2 h prior to biopsy taking. The tumor area positive for each marker, the colocalization of the different markers and the distribution of the markers in relation to the blood vessels were assessed by semiautomatic quantitative analysis.ResultsMCT1 staining was present in hypoxic (pimonidazole stained) as well as non-hypoxic areas in almost equal amounts. MCT1 expression showed a significant overall correlation (r = 0.75, p < 0.001) and strong spatial relationship with CAIX. LDH-5 showed the strongest correlation with pimonidazole (r = 0.66, p = 0.002). MCT4 and GLUT-1 demonstrated a typical diffusion-limited hypoxic pattern and showed a high degree of colocalization. Both MCT4 and CAIX showed a higher expression in the primary tumor in node positive patients (p = 0.09 both).ConclusionsColocalization and staining patterns of metabolic and hypoxia-related proteins provides valuable additional information over single protein analyses and can improve the understanding of their functions and environmental influences.

【 授权许可】

CC BY   
© Rademakers et al; licensee BioMed Central Ltd. 2011