Expression And Significance Of TTF-1,Pax-8 And TSHR In Papillary Thyroid Carcinoma

Objective: Over the past 20 years,the incidence of thyroid cancer in China has increased significantly,with an average annual growth of about6.2%.According to the "2012 Chinese cancer registry annual report" report,in the national cancer registries,the incidence of thyroid cancer accounted for tenth,6.54/10 million;and occupy eighth place in women,up to 10.09/10million;the incidence of male and female ratio is 1:3.2.More than 90% of thyroid cancer is differentiated thyroid carcinoma(DTC),and papillary thyroid carcinoma is the most common pathological type of thyroid carcinoma[1].At present,the treatment of PTC is the most important surgical treatment,endocrine therapy and radioactive I131 treatment is also very critical.Postoperative endocrine therapy can reduce the recurrence and metastasis of thyroid cancer.Studies have shown that TTF-1 is a molecular weight of 38 kD DNA binding protein,belongs to a member of the transcription factor family plays an important role in the process of growth and development of thyroid,specificity protein gene promoter TTF-1 binding sites or enhancer region,of thyroid specific genes(such as Tg,TPO,TSHR and NIS)transcription is regulated.Pax-8 belongs to a member of the transcription factor family,which expresses a nuclear protein that regulates the growth and differentiation of thyroid follicular cells and the expression of thyroid specific genes.Specific transcription factor transcription of specific genes usually depends on a series of cells,such as thyroid transcription factor 1(Thyroid,transcriptionfactor-1,TTF-1)and transcription factor gene encoding the 8 box(Paired-domaintranscription factor,Pax-8).TSHR is a member of G protein coupled receptor family,large protein molecules composed of alpha beta two subunit polypeptides,which mainly exists in the thyroid follicular cell membrane,is the main site of action of TSH.The results showed that the expression ofTSHR decreased with the decrease of thyroid tissue differentiation.TSH and TSHR on the cell surface after the combination of alpha subunit and cell surface G protein coupling and activation of cAMP is mediated by G protein(adenylate cyclase),so that the increase of intracellular c AMP,cAMP further activation of PKA(protein kinase A),activation of PKA after activation of specific nuclear transcription factors,such as TTF-1(thyroid specific transcription factor-1),TTF-2(thyroid specific transcription factor-2),Pax-8(a gene box 8)or the phosphorylation to regulate the function of thyroid function,further affect the expression of thyroid specific cell surface receptors,such as TG,TSHR,NIS,TPO,etc.Therefore,the study of thyroid transcription factor can indirectly reflect the quantity and activity of TSHR.The expression of TSHR in thyroid cancer research more,the results were not consistent,few studies on the transcription factor of the report,and the location and expression difference of TTF-1 and Pax-8 in thyroid benign and malignant tumors of the still controversial.The relationship between transcription factors(TTF-1,Pax-8)and TSHR has not been studied in china.This topic through the immunohistochemical SP method of thyroid papillary carcinoma(PTC)tissue and nodular goiter(NG)expression of TTF-1,Pax-8and TSHR in tissues,and study the correlation of TTF-1,Pax-8 and TSHR,for the occurrence and development of papillary thyroid carcinoma,diagnosis and provide a theoretical basis for the the treatment effect.Methods: This experiment collected glands East Hospital District Second Affiliated Hospital of Hebei Medical University from 2014 08 to 201607 resection month surgery thyroid tissue specimens from 98 patients,including 56 cases of thyroid papillary carcinoma,42 cases of nodular goiter.All patients with thyroid cancer were not treated with chemotherapy.Differentiated thyroid cancer was divided into 38 stages according to the standard TNM,I stage,II stage,III stage,stage,and IV stage in 5 cases.There were 38 cases with lymph node metastasis and no lymph node metastasis in 18 cases.All tissues were taken 4 μm thickness of the continuous section of the 7,in which a total of 1 slices of conventional HE staining for morphologicalobservation,the remaining 6 were used for TTF-1,Pax-8 and TSHR immunohistochemical staining and negative control.SP was used to detect the expression of TTF-1,Pax-8 and TSHR in papillary thyroid carcinoma and nodular goiter.SPSS statistical software was used to analyze the data by chi square test,nonparametric rank test and rank correlation method.Test standard for P > 0.05 was statistically significant.Results:1 TTF-1 is expressed in the thyroid gland.Papillary thyroid carcinoma(PTC),nodular goiter(NG)positive expression of TTF-1 in tissue were 80.4%and 95.2%,the positive rate of thyroid nodules was higher than that in papillary thyroid carcinoma,there was no significant difference of the positive expression of TTF-1 Wilcoxon in both the W test(Z=-0.892,P=0.372 P>0.05).I/II papillary thyroid cancer group had a higher proportion of papillary thyroid cancer than III/IV,the difference was statistically significant(P<0.05),indicating that the reduction of TTF-1,the worse the clinical prognosis.In addition,we found that there was no significant difference in the other pathological parameters,such as lymph node metastasis,tumor size,gender,age and TTF-1.It cannot be thought that the expression of TTF-1 is related to these factors.2 The expression of Pax-8 in thyroid cells is the nucleus and(or)cytoplasm.Expressed in two cases,but there are significant differences in the expression of PTC in the main form: karyoplasmic cell co expression,and the difference was statistically significant(Z=-5.689,P=0.000,P<0.01);NG was mainly expressed in the nucleus,the difference was statistically significant(Z=-6.256 P= 0.000,P<0.01).3 TSHR was mainly expressed in the basal side of the cell membrane in the thyroid gland cells.In addition,there was a little expression in the cytoplasm of papillary thyroid carcinoma cells.However,the intensity of papillary thyroid carcinoma was less than that of nodular thyroid tissue.The positive rate in 56 cases of PTC tissues was 83.9%,the positive and strong positive expression rate was 48.2%;42 cases of nodular goiter,the positiverate was 100%,positive and strong positive expression rate accounted for85.7%;the two groups of data in Wilcoxon W test with statistical significance,that the expression of nodular goiter.The TSH receptor is higher than that of papillary thyroid carcinoma.TNM staging: I / II positive accounted for 36/40,the positive expression rate was 90%,stage III / IV positive accounted for11/16,the positive expression rate was 68.8%.The positive expression rate increased with stage level,decreased by Wilcoxon W test,the difference has statistical significance and clinical analysis of the expression level of TSHR,that the expression level of TSH receptor is lower,the worse the prognosis.In addition,lymph node metastasis,gender,tumor size,age,and TSHR were not statistically significant.It is not thought that the expression of TSH receptor is related to these factors.4 Spearman correlation analysis on the expression of TTF-1 and TSHR in papillary thyroid carcinoma,the expression was positively correlated with TSHR expression of TTF-1(r=0.520,P=0.000),when the decrease in TTF-1expression in papillary thyroid carcinoma,the expression of TSHR also decreased.In two patients with nodular goiter(r=0.649,P=0.000),there was a positive correlation between the two.The Pax-8 and TSHR in papillary thyroid carcinoma cell nuclear cytoplasmic co expression were analyzed by Spearman correlation analysis: P = 0.069,P>0.05,according to α=0.05 level,and still can not believe that in papillary thyroid carcinoma Pax-8 and TSHR nucleus and cytoplasm were correlated.Conclusion:1 TTF-l can be well expressed in benign and malignant lesions of thyroid gland,and can be used to detect the source of tumor by TTF 1.2 Pax-8 is mainly expressed in the nucleus and cytoplasm in PTC,and has good value in differential diagnosis,suggesting that Pax-8 has potential application value as PTC diagnostic marker.3 The expression of TSHR in PTC was distributed from negative to positive,which provided a theoretical basis for endocrine therapy,and also provided help for clinical treatment.4 PTC and NG in both TTF-1 and TSHR have a strong positive correlation,to provide a theoretical basis for endocrine therapy.