| Part one Diagnostic value of CU,UE,US-FNAB and combination of BRAF V600 E mutation detection for thyroid nodules of TI-RADS4-5 categoriesObjective: To investigate the value of conventional ultrasound(CU),ultrasound elastography(UE),ultrasound-guided fine-needle aspiration biopsy(US-FNAB),v-raf murine sacoma viral oncogene homolog B1(BRAF)V600E mutation detection and different combination of those diagnostic methods for the differential diagnosis of benign and malignant thyroid nodules.Methods: From June 2015 to March 2016,82 patients with 86 thyroid nodules from Affiliated Hospital of North Sichuan Medical College were enrolled.All the nodules were examined by CU and were classificated as TI-RADS 4-5 categories according to the thyroid imaging reporting and data system(TI-RADS)proposed by Horvath et al,then these nodules were evaluated by UE,US-FNAB and BRAF V600 E mutation detection from the puncture samples.Patients with dissatisfied ultrasound images,cytopathology diagnosises and amplified DNA products were excluded.Because there were a lower risk of malignance in grade 4a nodules and a higher risk of malignance in grade 4b and grade 5 nodules,nodules with CU features of grade 4a tended to be classified as benign,and those of grade 4b-5 tended to be classified as malignant.Nodules with a elastic classfication of grade 0-2 were evaluated as benign,and those of grade 3-4 were evaluated as malignant according to a five classes scale.Histopathology after the operations and the clinical follow-up results were taken as the reference standard.The differential diagnostic value of CU,UE and the combination of the two methods in the whole nodules of TI-RADS 4-5 categories were comparatively analysized.Then the grade 4a and grade 4b-5 were divided into two groups,and the differential diagnostic values of UE,US-FNAB,US-FNAB combined with UE and US-FNAB combined with BRAF V600 E mutation detection were comparatively studied.Results: 1)Among the 86 thyroid nodules of TI-RADS 4-5 categories,44 were finally diagnosed as malignant and 42 were benign.The CU features of solid component with hypoechogenicity,ill-difined borders,irregular shapes,taller-than-wide shape and microcalcifications were significant in the differential diagnosis(P<0.05).There was no significant difference in size,envelope and blood flow in benign and malignant nodules(P>0.05).2)The method that CU features of grade 4a tended to be classified as benign and those of grade 4b-5 tended to be classified as malignant was compared with UE and the combination of the two ways with higher specificity(95.2%)and lower sensitivity(52.3%)in diagnosing the whole nodules(P<0.05).And the combination of the two ways could be obtained high sensitivity(81.8%)and moderate diagnostic value(AUC=0.719).3)Among the 61 thyroid nodules of TI-RADS 4a categories,21 were finally diagnosed as malignant and 40 were benign.The differential diagnosis sensitivity of US-FNAB combining with UE was 66.7%,which was higher than that of UE(61.95%)and US-FNAB(33.3%).The specificity of US-FNAB combining with UE was 62.5%,which was lower than that of UE(65.0%)and US-FNAB(90.0%).The highest sensitivity(81.0%),specificity(90.0%)and the largest area under the ROC curve(AUC=0.855)were identified from the combination of US-FNAB and BRAF V600 E mutation detection(P<0.05).4)Among the 25 thyroid nodules of TI-RADS 4b-5 categories,23 were finally diagnosed as malignant and 2 were benign.The true-positives of UE,US-FNAB,US-FNAB combined with UE and US-FNAB combined with BRAF V600 E mutation were 20,18,22 and 21,respectively.May be influenced by the limitations of UE,too little benign cases,selection bias and other factors,there were 3 cases which were diagnosed as benign by UE and 1case which were diagnosed as benign by US-FNAB combined with UE were all diagnosed as malignant in the end.This situation caused that there was no true-negative case.For the nodules of grade 4b-5 with a high risk of maligannce,US-FNAB and US-FNAB combined with BRAF mutation detection could get a high diagnostic value.Those AUC were respectively 0.891 and 0.957 with statistically significant difference(P<0.05).Conclusions: TI-RADS based on CU was in favour of screening those nodules with greater likelihood of malignancy.CU combined with UE could further determine the appropriate nodules to undergo US-FNAB and avoid excessive puncture.When multiple CU signs were obviously malignant whereas UE evaluated as benign,it was suggested that CU should be used as a guide to avoid missed diagnosis.To effectively combine US-FNAB and BRAF V600 E mutation detection could significantly increase the accuracy of puncture diagnosis,avoid repeated puncture and make a early diagnosis for papillary thyroid carcinoma.Part two The differential expression of miR-221 in benign and maligant thyroid nodules of TI-RADS4-5 categories and its correlation with BRAF V600E mutationObjective: To comparatively analysize the differential expression of miR-221 in benign and maligant thyroid nodules of TI-RADS4-5 categories and in papillary thyroid carcinomas(PTCs)whether accompanied with BRAF V600 E mutation.Methods: From June 2015 to March 2016,82 patients wiith 86 thyroid nodules from Affiliated Hospital of North Sichuan Medical College were enrolled.All the nodules were examined by CU and classificated as TI-RADS 4-5 categories according to the TI-RADS proposed by Horvath et al,then these nodules were evaluated by UE,US-FNAB and BRAF V600 E mutation detection and miR-221 detection from the puncture samples.Patients with dissatisfied ultrasound images,cytopathology diagnosises and amplified DNA products were excluded.Histopathology after the operations and the clinical follow-up results were taken as the reference standard.BRAF V600 E mutation was detected by polymerase chain reaction(PCR)in one puncture sample.MiR-221 expression was quantified by real-time polymerase chain reaction(RT-PCR)in another puncture sample.The results were statistically analyzed and evaluated.Results: 1)Among the 44 malignant nodules,42 were PTCs and 2 were Diffuse Large B-cell Lymphomas.31 BRAF V600 E mutation positive nodules were all proved to be PTCs after operation.There was significant difference of BRAF V600 E mutation between benign and malignant thyroid nodules(P<0.001).2)The relative expression of miR-221 was significantly higher in 44 malignant nodules(P<0.05).3)The 31 BRAF V600 E mutation positive nodules were obtained higher relative expression of miR-221 than the 55 BRAF V600 E mutation negative nodules(P<0.05).4)In the 42 PTCs, there was no significant difference of relative expression of miR-221 between PTCs with BRAF V600 E mutation and PTCs without BRAF V600E mutation(P>0.05).Conclusions: The relative expression of miR-221 could increase in malignant thyriod nodules.MiR-221 detection in puncture samples could provide another diagnostic thinking for preoperative diagnosis of thyroid carcinomas.The relative expression of miR-221 had no significant difference in the papillary thyroid carcinomas whether accompanied with BRAF V600 E mutation.Nevertheless,the relationship between miR-221 expression and BRAF V600 E mutation in other pathological types of thyroid carcinoma could not be excluded. |
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