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Expression Of Sodium/Iodide Symporter(NIS) In Differentiated Thyroid Cancer And Its Clinical Significance

Posted on:2015-02-06Degree:MasterType:Thesis
Country:ChinaCandidate:D L ShiFull Text:PDF
GTID:2254330428974200Subject:Surgery
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Objective: In recent20years, thyroid cancer has become one of therapid growth of malignant solid tumors. In thyroid cancer the incidence whichaccounts for more than90%is differentiated thyroid cancer (DTC).Differentiated thyroid cancer is an important type of our clinical treatment andresearch. The survival rate after operating is higher, but there are still somepatients whose tumors will be metastasis. A small amount of residual glandand metastatic lesions of differentiated thyroid carcinoma postoperative can beradioiodine therapy. Therefore, radioactive iodine therapy is a primary meanof differentiated thyroid cancer postoperative therapy. Because the iodine isconcentrated in thyroid cells by sodium iodide symporter (NIS) with iodineuptake against the concentration of iodine and DTC retains a part of normalfunction of the thyroid cells with ability of uptake iodine, which has becomethe theoretical basis of differentiated thyroid cancer131I therapy. In normalthyroid tissue NIS is distributed only in a few follicular cells’ basalmembranes, whereas the basolateral membrane of thyroid follicular cells isjust the main part of playing function of NIS to uptake iodine. Studies suggestthat the amount of NIS distribution in thyroid cell membranes was positivelycorrelated with the amount of thyroid cells concentrating radioiodine. Thyroidadenoma showed an intensity of NIS expression similar to that of normalthyroid adjacent thyroid carcinoma; whereas there is a strong NIS expressionin primary hyperthyroidism; undifferentiated carcinoma showed noexpression or weaker intensity; Medullary thyroid carcinoma derives fromparafollicular cell, which is not follicular epithelial cell, so it had noexpression; About the expression of NIS of differentiated thyroid cancer,relevant research results are not the same, or even draw the opposite results.In this study, immunohistochemical methods for follicular cell-deriveddifferent thyroid tissue staining was performed, to observe the expression conditions of NIS of different thyroid tissue, particularly differentiatedthyroid cancer, to discuss the correlation between the expression of NIS indifferentiated thyroid cancer and its ability of uptake iodine and provide atheoretical basis for131I radiation therapy.Methods: We collect139cases filed specimens paraffin block fromthyroid carcinoma tissue surgically removed from the department of pathologyof Second Hospital of Hebei Medical University from October2012toOctober2013. It includes papillary carcinoma (127cases), follicularcarcinoma (7cases), anaplastic carcinoma (5cases). The control groups wereanother30cases thyroid tissue adjacent thyroid cancer and48cases filedspecimen paraffin blocks from benign thyroid disease tissue surgicallyremoved at the same period, including (23cases) thyroid adenoma and (25cases) primary hyperthyroidism. All patients with thyroid disease were notinclude the implementation of preoperative chemotherapy, radiation and othertreatments. All thyroid tissue paraffin blocks were cut into3pieces of4μm-thick serial sections, in which1piece was used for conventional HEstaining for pathological morphology, the remaining2pieces were used forNIS immunohistochemical analysis and negative control. The expression ofNIS in different thyroid tissues was detected by SP method and was analyzedcombining with clinically relevant data. SPSS13.0statistical software wasused for data analysis from the Kruskal-WallisH test and Wilcoxon rank sumtest. Test criterion for P <0.05was statistically significant.Results: The positive staining of NIS was observed only in thebasolateral membrane of a part of follicular cells in thyroid tissues adjacentthyroid cancer; whereas the positive staining of NIS in primaryhyperthyroidism was still mainly in the membrane of a large number offollicular cells; in thyroid adenoma, the positive staining of NIS in thecytomembrane of follicular cells was similar to that of thyroid tissue adjacentthyroid cancer, whereas there was a part of staining in the cytoplasm. Indifferentiated thyroid cancer tissues, the positive staining of NIS was mainlyshown in the cytoplasm of follicular cells. Besides, there were also a part of staining in the membrane. Anaplastic carcinoma tissues showed almostnegative staining. In cell membranes and (or) cytoplasmic staining as positivecells judgment standard: there was a positive rate of87.05%in139cases ofthyroid cancer. There was a positive rate of47.83%in23cases of thyroidadenoma. There was a positive rate of100%in25cases of primaryhyperthyroidism. There was a positive rate of56.67%in30cases of thyroidtissue adjacent thyroid cancer. The staining intensity of four different thyroidtissues indicated significant in four groups from the Kruskal-Wallis H test.Multiple comparisons of staining intensity were carried out in thyroid cancer,thyroid adenoma, primary hyperthyroidism and thyroid tissues adjacentthyroid cancer from the Wilcoxon rank sum test. Between others pairwisedifferences in staining intensity of NIS were significantly, except statisticaldifference between thyroid adenoma and thyroid tissues adjacent thyroidcancer in staining intensity was not significantly. That staining intensity ofNIS of the primary hyperthyroidism was higher than thyroid cancer, whereasthe staining intensity of thyroid cancer was higher than the thyroid adenomaand thyroid tissues adjacent thyroid cancer.According to the extent of differentiation, we can divide thyroid cancerinto anaplastic thyroid cancer and differentiated thyroid cancer. There was apositive staining rate of20%in5cases of anaplastic thyroid carcinoma;whereas the positive rate of134cases differentiated thyroid cancer was89.55%. There was statistical significance between anaplastic anddifferentiated thyroid cancer from the Wilcoxon rank sum test, that thestaining intensity of NIS of the differentiated thyroid cancer was higher thanthe anaplastic thyroid cancer.Further to the cell membrane staining as positive cells judgment standard:there was a positive rate of14.53%of cell membrane of NIS in134cases ofdifferentiated thyroid cancer. There was a positive rate of30.43%of cellmembrane of NIS in23cases of thyroid adenoma. There was a positive rateof100%of cell membrane of NIS in25cases of primary hyperthyroidism.There was a positive rate of46.67%of cell membrane of NIS in30cases of thyroid tissue adjacent thyroid cancer.There was a positive rate of0%of cellmembrane of NIS in5cases of anaplastic thyroid cancer. Therefore, thestaining intensity of NIS in cell membrane of four different thyroid tissuesindicated significant in four groups from the Kruskal-Wallis H test. Multiplecomparisons of staining intensity of NIS in cell membrane were carried out indifferentiated thyroid cancer, thyroid adenoma, primary hyperthyroidism andthyroid tissues adjacent thyroid cancer from the Wilcoxon rank sum test.Between others pairwise differences in staining intensity of NIS in cellmembrane were significantly, except statistical difference between thyroidadenoma and thyroid tissues adjacent thyroid cancer in staining intensity ofcell membrane was not significantly. That staining intensity of NIS in cellmembrane of the primary hyperthyroidism was higher than thyroid adenomaand thyroid tissues adjacent thyroid cancer, whereas the staining intensity ofNIS in cell membrane of the thyroid adenoma and thyroid tissues adjacentthyroid cancer was higher than differentiated thyroid cancer.Conclusion:1. The distribution differences of NIS in different thyroid tissuesuggest that the NIS functional protein may be locating in the cell membrane.2. It distributed from negative to positive in NIS protein of cellmembrane of differentiated thyroid cancer. This study provides a theoreticalbasis for individualized131I radiation therapy.3. The positive expression level of NIS protein in cell membrane ofdifferentiated thyroid cancer may indirectly predict the ability of uptake iodineand the effect of131I radiotherapy of differentiated thyroid cancer.
Keywords/Search Tags:Thyroid carcinoma, Immunohistochemistry, Sodium/Iodide Symporter, 131I radiation therapy, Differentiation
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