| Objective:Papillary thyroid carcinoma (PTC) is the most common type of thyroid carcinoma. Sodium iodide symporter (NIS) protein expressed in the thyroid follicular cell membrane, which is not only important for iodine uptake but also is the basis of synthesis of thyroid hormones, the premise of radioactive131I treatment and thyroid radionuclide imaging. This study will detect NISmRNA and NIS protein in PTC and normal thyroid tissue. Clinical data was retrospectively reviewed. We will explore the correlation between the expression of NIS and clinicopathological parameters of PTC. Meanwhile the correlation between BRAFV600E mutation and the expression of NIS is also involved. We hope we can provide an avenue for the prediction of radioactive131I treatment through the study.Methods:We choose110PTC treated in Tianjin cancer hospital from March2011to February2012. In the operation we reserve part of fresh thyroid carcinoma tissue of all patients and normal tissue of75patients. BRAFV600E mutation was detected by polymerase chain reaction and DNA sequencing assays. Meanwhile NISmRNA quantified by real-time RT-PCR. The paraffin blocks of60PTC and46normal tissue were collected and NIS protein evaluated by immunohistochemistry. Clinical data was retrospectively reviewed and evaluated using SPSS17.0statistical software package. Results of real-time RT-PCR were expressed as Mean±SD. NISmRNA expression was analyzed with Analysis of Variance (ANOVA), correlation tests and t tests. χ2tests and t tests were used to compare the expression of NIS protein. P<0.05was considered statistically significant.Results:1、NIS mRNA levels tended to be significantly lower in PTC (ΔCT=9.52712±2.494994) than in normal thyroid tissue(ΔCT=6.83057±1.547448). The quantity of NIS mRNA expression in PTC is0.383160times that in normal thyroid tissue.2、PTC patients showed different levels of serum TSH at the time of surgery varying from0to greater than100mU/ml. No relationship was found between serum TSH at the time of thyroidectomy and the levels of expression of NIS mRNA. PTC patients showed different levels of serum Tg at the time of surgery varying from0to greater than1000mg/dL. No relationship was found between serum Tg at the time of thyroidectomy and the levels of expression of NIS mRNA3、The presence of BRAFV600E mutation was found in69of PTC (62.7%).It was only detected in PTC and not detected in75normal thyroid tissue. There was a significant difference at BRAFV600E mutation rate in age groups≤30,30-60,≥60(25.0%,62.8%and81.2%respectively). But statistical data did not show any correlation between BRAFv600E mutation and other clinicopathologic parameters in PTC. BRAFV600E mutation rate in PTC coexisting Hashimoto’s thyroiditis is42.5%.And the rate is72.1%in PTC coexisting nodulor goiter. These results were both significant different with PTC not coexisting the benign thyroid lesion.4、NIS mRNA levels tended to be significantly lower in BRAFV600E mutated PTC (ΔCT=10.17494±2.254310) than in BRAFV600E non-mutated PTC (ΔCT=8.61430±2.556094). The quantity of NIS mRNA expression in BRAFv600E mutated PTC is0.263618times that in BRAFV600E non-mutated PTC.5、No relationship was found between expression of NIS mRNA and gender, lymph node metastasis, extra thyroidal invasion, stage. There was no significant difference between expression of NIS mRNA in PTC coexisting Hashimoto’s thyroiditis, PTC coexisting nodular goiter and PTC not coexisting the benign thyroid lesion. Expression of NIS mRNA was lower in PTC patients over60years old and in tumors larger than2centimetre.6、Immunohistochemistry show that the positive expression rate of NIS protein in PTC and normal thyroid tissue were81.7%(49/60) and43.5%(20/46).The positive expression rate between the two groups exist significant differences.7、Serum TSH and Tg were not found significant difference between the NIS protein positive group and NIS protein negative group.(NIS protein positive group: TSH=2.9144±2.02870mU/L,Tg=49.86±55.291mg/dL;NISproteinnegativegroup:TSH= 3.1498±1.88362mU/L,Tg=64.07±48.703mg/dL)8、The positive expression rate of NIS protein in BRAFV600E mutated PTC is70.3%,while in BRAFV600E non-mutated PTC is91.3%.But there was no significant difference.9、No relationship was found between expression of NIS protein and age, gender, tumor size, lymph node metastasis, extra thyroidal invasion, stage.Conclusion:1、Our results indicated that in cells from PTC,low NIS mRNA expression coexists with abundant intracellular NIS protein.NIS expression alterations may occur in transcriptional and post-ranscriptional levels.The related literatures show that NIS protein may be unable to migrate to the basolateral membrane in PTC.2、The thyroid function of our cases is normal and none patients were on thyroid hormone suppressive therapy at the time of surgery in our study, so NIS mRNA and NIS protein levels had no correlation with preoperative TSH and Tg levels. It also proved that our results were independent of serum TSH and Tg levels which could affect NIS mRNA and protein expression.3、NIS mRNA levels tended to be significantly lower in BRAFv600E mutated PTC than in BRAFV600E non-mutated PTC. But same result was not obtained in NIS protein study. We suggest that low expression of NIS mRNA had correlation with BRAFV600E mutation.4、Expression of NIS mRNA was lower in PTC patients over60years old and in tumors larger than2centimetre. No relationship was found between expression of NIS mRNA and gender, lymph node metastasis, extra thyroidal invasion, stage. There was no correction between expression of NIS protein and age, gender, tumor size, lymph node metastasis, extra thyroidal invasion, stage in our study. We suggest that expression of NIS mRNA had correlation with tumor size and the age of PTC patients.5、The presence of BRAFV600E mutation was found in69of PTC (62.7%) in our study. It was only detected in PTC and not detected in normal thyroid tissue. Differences in genetic backgrounds might explain the difference of BRAFV600E mutation rate. The rate in the study is higher than the results of western countries but lower than those of Korean. BRAFV600E mutation rate is different in different age groups.The rate is low in young patients group while it is high in eldly patients group. BRAFV600E mutation may be a time-cumulative process. The rate in PTC coexisting Hashimoto’s thyroiditis is low but high in PTC coexisting nodular goiter. |
PDF Full Text Request