Expression Of IL-17 And The Clinical Significance Of Vascular Proliferation In Hashimoto's Thyroiditis With Benign And Malignant

Objective: To observe the ultrasonographic features and pathological changes of the thyroid in the progression of malignant transformation of Hashimoto's thyroiditis(HT),and to analyze the expression of IL-17 in Hashimoto's thyroiditis(HT),Hashimoto's thyroiditis with benign nodule(HTB),Papillary thyroid carcinoma(PTC)and Hashimoto's thyroiditis with carcinoma(HTC)and its clinical significance.Methods: The HT patients,HTB patients,PTC patients,and HTC patients who were diagnosed by thyroid ultrasound-guided biopsy or routine pathological diagnosis from Department of Thyroid Surgery from May 2015 to December 2017 were collected and enrolled in this study.Healthy volunteers were served as the healthy controls(HC).Ultrasonography was used to observe the ultrasonic characteristic of the thyroid during the malignant transformation progression of Hashimoto's thyroiditis.Hematoxylin and Eeosin(H&E)staining was used to observe the pathological changes of the thyroid gland.Serum IL-17 and VEGF levels were measured by enzyme-linked immunosorbent assay(ELISA).Immunohistochemistry(IHC)and immunization were performed.The concentrations of IL-17 in serum and the levels of IL-17 DNA in the puncture tissues from HTB and HTC patients were analyzed.The receiver operating characteristic curve(ROC)was used to distinguish HTB and HTC patients,and the Area Under Curve(AUC)was analyzed to designate the efficacy of distinguish ability.Results:(1)According to the strict inclusion criteria and exclusion criteria,a total of 50 HT patients,30 HTB patients,60 PTC patients,and 30 HTC patients were included in this study.All participants signed the study protocol and the informed consent form.(2)In addition to diffuse hypoechoic,grid-like strong echoes and other symptoms of Hashimoto's thyroiditis were presented in HTC patients.The nodules have the following characteristics: the unclear boundary,the irregular morphology,aspect ratio greater than 1,solid hypoechoic nodules,the inhomogenous internal echo,more visible microcalcification or coarse calcification,partial calcification of the posterior echo attenuation.The blood flow of HTC patients was richer than that of the normal control group.The detection rate of peak systolic velocity,resistance index,and peripheral silent halo,microcalcification,aspect ratio >1,hypoechoic,and suspicious cervical lymph node metastasis were also higher in the HTC patients than those in the control group.(3)High-impedance blood flow signals were measured in thyroid nodules of patients with HTC,while low impedance flow signals were measured by spectral Doppler ultrasound in the thyroid nodules of patients with HTB.Serum IL-17 level was significantly higher in Hashimoto's thyroiditis group(8.08±1.19 pg/ml)than that in the control group(5.96±1.37 pg/ml)(P<0.001).Compared with the HTB patients(8.52±0.91 pg/ml),serum IL-17 levels in the PTC group(9.20±1.33 pg/ml)and HTC group(10.18±1.12 pg/ml)were both significantly elevated(both P<0.001).Compared with the healthy control group(165.67±15.88 ng/ml),the serum VEGF level was significantly higher in the HT group(188.00±26.29 ng/ml)(P<0.001).Compared with HTB group(198.67±23.35 ng/ml),serum VEGF levels were significantly elevated in the PTC group(227.08±27.51 ng/ml)and HTC group(233.70±9.21 ng/ml)(both P<0.001).During the malignant transformation of HT,there was a significant positive correlation between serum VEGF levels and IL-17 levels(correlation coefficient R=0.456;P<0.0001;95% confidence interval(CI): 0.341-0.561),and the correlation equation is: Y = 8.735 X + 130.8.(4)Serum IL-17 levels achieved an AUC of 0.904 in patients with HTB and HTC(95% confidence interval: 0.831-0.976),and VEGF levels in the serum achieved an AUC value of 0.885 in HTB patients and HTC patients(95% confidence interval: 0.801-0.969),which achieved an effective diagnosis of HTC patients.(5)Protein VEGF expression mainly presented a negative and weakly positive expression in the HT patients and HTB patients,while the positive and strong positive expressions are predominant in PTC patients and HTC patients.These data show that with the malignant transformation of Hashimoto's thyroiditis,the expression level of protein VEGF is gradually increased.(6)Compared with HTB patients,the expression level of MVD was significantly higher in the PTC and HTC patients,and the difference was statistically significant.Conclusions:(1)Hashimoto's thyroiditis with papillary carcinoma showed unique features on the ultrasound two-dimensional sonogram.(2)During the malignant transformation of Hashimoto's thyroiditis,the levels of serum IL-17 and VEGF showed gradually increasing trend;IL-17 and VEGF may be involved in the progression from Hashimoto's thyroiditis,Hashimoto's thyroiditis and benign nodules to Hashimoto's papillary carcinoma.(3)During the malignant transformation of Hashimoto's thyroiditis,there was a significant positive correlation between serum VEGF levels and IL-17 levels.(4)Serum levels of IL-17 and VEGF can significantly distinguish Hashimoto's thyroiditis with benign nodules from Hashimoto's thyroiditis with papillary carcinoma.Therefore,serum levels of IL-17 and VEGF can be used to diagnose the Hashimoto's thyroiditis with papillary carcinoma.