A Correlation Study between DCE-MRI Quantitative Parameters and Immunohistochemical Labeling Indices in Nasopharyngeal Carcinoma
Yunbin Chen 1, Meng Liu2, Dechun Zheng1, Qiuyuan Yue1, Xiaoxiao Zhang1, Hao Lin1, Weibo Chen 3, Queenie Chan4, Wang Ren1, and Xiangyi Liu1

1Fujian Provincial Cancer hospital, Fuzhou, China, People's Republic of, 2Fujian Provincial Cancer Hospital, Fuzhou, China, People's Republic of, 3Philips Healthcare, Shanghai, China, People's Republic of, 4Philips Healthcare, Hong Kong, China, People's Republic of

Synopsis

We assessed correlations between 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). We found that HIF-1α positive group was significantly correlated with VEGF positive expression and MVD count respectively. Ktrans and Kepwas positively associated with HIF-1α positive expression, VEGF positive expression and MVD respectively .There were significantly positive correlations between vp and the VEGF expression, MVD count respectively. However, there were no significant relationship between the Ki67 expression and any DCE-MRI quantitative parameters in our study.

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 (Ktrans, Kep ,Ve and Vp) 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). Ktrans 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).Kep 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 vp 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.

Acknowledgements

This study is partly supported by the Natural Science Foundation of Fujian Province (Grant No. 2012J01330) and partly supported by the National Clinical Key Specialty Construction Program and Key Clinical Specialty Discipline Construction Program of Fujian, P.R.C.

References

[1]. Foote RL, Weidner N, et al. Int J Radiat Oncol Biol Phys.2005, 61(3): 745-753.

[2]. Chen YH. Med Oncol. 2014; 31(12): 304.

[3]. Guang-Wu H. Laryngoscope. 2000; 110(12):2066-9.

[4]. Forsythe JA. Mol Cell Biol. 1996; 16(9): 4604–13.

Figures

Figure 1 (a,b,c,d). Histograms of the expression index distribution of HIF-1α, VEGF, MVD, Ki67

Table 1 Relationship between DCE-MRI quantitative parameters and Immunohistochemical Labeling Indices



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
2886