Preliminary Study Of Functional Magnetic Resonance Imaging In Evaluating Pathological Features And Hypoxic Microenvironment Of Cervical Squamous Cell Carcinoma

Objective To evaluate the correlation of quantitative parameters of dynamic contrastenhanced magnetic resonance（DCE-MR）and diffusion-weighted imaging（DWI）with the pathological features and the expression of hypoxia-inducible factor 1-α（HIF-1α）in patients with cervical squamous cell carcinoma（CSCC）.Methods A total of 81 patients with CSCC in Liaoning Cancer Hospital & Institute from 2015 to 2017 were retrospectively included.According to FIGO 2009 clinical stage,53 cases were stage IB,27 cases were stage IIA,and 1 case was stage IIB.CSCC was confirmed as by biopsy.The patients examine enhanced computed tomography（CT）scan,pelvic magnetic resonance（MR）scan,diffusion-weighted imaging（DWI）and dynamic enhanced magnetic resonance imaging（DCE-MRI）before treatment.The patient’s age,clinical stage,lymph node metastasis（LNM）,lymphovascular space invasion（LVSI）,deep stromal invasion（DSI）and differential degree（DD）were collected.Measure DCE-MR parameters(K^trans,Kep and Ve)and ADC values.HIF-1α expression and Ki-67 expression were obtained by immunohistochemistry.The differences of HIF-1α expression and Ki-67 expression between patients with or without lymph node metastasis,vascular tumor thrombus,interstitial infiltration depth and pathological differentiation were compared by rank sum test.The diversity of DCE-MRI quantitative parameters K^trans,Kep,Ve and DWI parameters ADC values between groups with or without lymph node metastasis,vascular tumor thrombus,interstitial infiltration depth and pathological differentiation were compared by rank sum test.DCE-MRI quantitative parameters K^trans,Kep,Ve and DWI parameters ADC values and HIF-1α expression,Ki-67 expression were analyzed by non-parametric Spearman correlation analysis,using SPSS 25.0 software,P < 0.05 The difference was statistically significant.Result 1.HIF-1α expression: 12 patients（14.8%）had score 0,2 patients（2.5%）had score 1,11 patients（13.6%）had score 2,6 patients（7.4%）had score 3,18 patients（22.2%）had score 4,25 patients（30.9%）had score 6,and 7 patients（8.6%）had score 9.Low expression was observed in 49 patients（60.5%）and high expression in 32 patients（39.5%）.Ki-67 expression: < 50%: 52（64.2%）,≥ 50%: 29（35.8%）2.In The expression of HIF-1α in CSCC patients was significantly different between groups with or without LNM（P=0.007）,LVSI（P=0.002）,DSI（P=0.003）and DD（P=0.021）.patients with LNM,HIF-1α expression was higher;in patients with lymphovascular space invasion,HIF-1α expression was higher than that in patients without vascular tumor thrombus;the deeper the deep stromal invasion,the higher the HIF-1α expression;and the lower the differential degree,the higher the HIF-1α expression.Ki-67 expression was different between lymph node metastasis and nonmetastasis groups（P = 0.005）,and Ki-67 expression was higher in patients with lymph node metastasis than in those without lymph node metastasis;Ki-67 expression was different between groups with stromal invasion depth ≥ 1/2 and stromal invasion depth < 1/2（P = 0.017）,and the deeper the depth of stromal invasion,the higher the Ki-67 expression.There was no significant difference in Ki-67 expression between the group with vascular tumor thrombus and the group without vascular tumor thrombus and between the poorly differentiated,moderately differentiated,and well differentiated groups（P > 0.05）.3.The K^trans（P=0.001）was significantly different between non-LNM and LNM groups.The other DCE and DWI parameters had no significant difference between the groups with or without LNM,LVSI,DSI and DD（P>0.05）.4.HIF-1α was positively correlated with Ki-67（r=0.249,P=0.025）.HIF-1α was positively correlated with K^trans and Kep（r=0.478,r=0.388,P=0.001）.There was no correlation between HIF-1α expression and Ve,ADC value.There was no correlation between Ki-67 expression and K^trans 、Kep and Ve.Ki-67 expression was negatively correlated with ADC（r =-0.359,P = 0.001）.Conclusion 1.HIF-1α is associated with LNM,LVSI,DSI and DD of cervical squamous cell carcinoma.Patients with LNM and LVSI,deeper the deep stromal invasion,and cervical squamous cell carcinoma with lower differential degree has a greater degree of malignancy,more severe tumor hypoxia,and higher HIF-1α expression.2.Ki-67 is related to lymph node metastasis and depth of stromal invasion in cervical squamous cell carcinoma.Cervical squamous cell carcinoma with deep stromal invasion has a high degree of malignancy,the more significant the cell proliferation,and the higher the Ki-67 expression.Ki-67 expression was positively correlated with HIF-1α expression,and hypoxia was more pronounced in tumors with significant cell proliferation.3.Functional magnetic resonance imaging parameters can predict HIF-1α and Ki-67 expression,and then assess the hypoxic microenvironment of the cervical squamous cell carcinoma.