Purpose To assess correlations between dynamic contrast-enhanced MRI (DCE-MRI) quantitative parameters with immunohistochemical labeling indices which reflect tumor hypoxia (HIF-1α), tumor angiogenesis (VEGF, MVD) and tumor proliferation (Ki67) in nasopharyngeal carcinoma(NPC), as well as the expression of HIF-1α, VEGF, MVD and Ki67.

Methods Sixty-eight patients(55 males and 13 females; average age, 45 years; range, 16-70 years) with NPC received DCE-MRI and nasopharyngeal biopsy before treatment. We performed MRI examinations on a 3.0 tesla (Achieva TX, Philips Healthcare, Best, The Netherlands) whole-body MR scanner system equipped with parallel radio frequency transmission using a 16-channel neurovascular coil. We investigated quantitative kinetic parameters (K^trans, K_ep ,V_e and V_p) by using DCE-Tool based on extended Tofts’ model.HIF-1α, VEGF expression, MVD and Ki67 expression were detected by immunohistochemistry(IHC) staining. MVD count was based on Weidner method [1].The expression of Ki67 was the percentage of positive staining cells. The expression of HIF-1α and VEGF were percentage multiplied by intensity scores. Finally, the correlations were analyzed by Spearman’s rank coefficient analysis. A p value ＜0.05 was considered statistical significance.

Results The representative expressions of immunohistochemical indices in NPC were shown in Figure1. HIF-1α positive group was significantly correlated with VEGF positive expression and MVD count respectively (γ=0.514, γ=0.571; P < 0.001). MVD was statistically correlated with the expression of VEGF positive group (γ=0.378). K^trans was positively associated with HIF-1α positive expression, VEGF positive expression and MVD respectively (γ=0.600, γ=0.534, γ=0.668; P <0.05).K_ep was positively associated with HIF-1α positive expression, VEGF positive expression and MVD count respectively (γ=0.485, γ=0.365, γ=0.441; P <0.05). There were significantly positive correlations between v_p and the VEGF expression, MVD count respectively (γ=0.362, γ=0.366; P <0.05) (table 1). However, there were no significant relationship between the Ki67 expression and any DCE-MRI quantitative parameters in our study.

Discussions Previous studies found that HIF-1α and VEGF were overexpression in NPC[2-3]. It was demonstrated that HIF-1α was a promoter to activate the VEGF [4]. VEGF is one of the most important factor in regulating tumor angiogenesis. Highly vascularized tumor tissue showed rapid enhancement after contrast injection. Characteristics of tumor blood vessels lead to high endothelial permeability and blood flow, which increased the DCE-MRI quantitative parameters.

Conclusions Hypoxia plays a key role in the growth and treatment of NPC. DCE-MRI quantitative parameters might be used to noninvasively assess tumor hypoxia and tumor angiogenesis in NPC. This provides an opportunity of applying DCE-MRI technique in early predicting treatment efficacy of NPC.