Expression Of Thyrotropin(TSH)-receptor In Thyroid Carcinoma And Its Clinical Significance

Objective: Thyroid cancer account for approximately 1% of all malignant tumors, which is more than 90% is differentiated thyroid cancer that includes papillary carcinoma, follicular carcinoma. For the treatment of differentiated thyroid cancer, is currently still the main way of surgical treatment. Currently,the main therapy of differentiated thyroid cancer, is still surgical treatment. In addition, because of differentiated thyroid carcinoma has a dependency on thyrotropin, patients usually need to be given levothyroxine for TSH suppression therapy to reduce the risk of thyroid cancer recurrence and metastasis by reduce the stimulation of thyroid tissue. However, TSH suppression therapy has many side effects including heart palpitations, sweating, fatigue, insomnia, irritability and other symptoms of thyroid toxicity, which ultimately lead to heart failure; besides, this therapy prone to occurrence of the elderly osteoporosis. Therefore, it is important to administration for individual. TSH receptor present in the membrane of thyroid follicular cell which is the major actual site of TSH. Studies suggest that most benign thyroid tumors showed an intensity similar to that of normal thyroid; undifferentiated carcinoma showed weaker intensity; medullary carcinoma derives from non-follicular epithelial cell, so it showed weaker intensity; in differentiated thyroid cancer various intensities of TSH receptor occurred. In this study, it were performed an immunohistochemical analysis that TSH receptor of derived from follicular thyroid carcinoma. We Observed TSH receptor stained intensity in surface of the follicular of thyroid carcinomas, discussed directive significance of clinical treatment, provided theoretical foundation of TSH suppression therapy.Methods: we collect 107 cases filed membrane block from thyroid tissue surgically removed from department of pathology of Second Affiliated Hospital of Hebei Medical University between January 2008 to June 2010. Age of 65 cases of papillary carcinoma patients is from 31 to 82; Age of 9 cases of filiteralveolar carcinoma is from 20 to 65; Age of 5 cases of anaplastic carcinoma is from 39 to 78; Age of 28 case adenoma is from 5 to 70; control group is normal tissue of adjacent adenoma. All patients with thyroid cancer were all did not preoperative radiation and chemotherapy. According to the UICC classification of thyroid cancer TNM staging criteria differentiated thyroid carcinoma were divided into group stageⅠ(29cases), group stageⅡ(23cases), group stageⅢ(18cases), group stageⅣ(4cases). Patients of lymph node metastases is 26 cases, patients without lymph node metastases is 53 cases. All thyroid tissue paraffin blocks were cut into 3 pieces of 4μm-thick serial sections, in which one piece of conventional HE staining pathological morphology, the remaining two pieces of immunohistochemical analysis of TSH-receptor and negative control. Using SP method to detect TSH receptor in thyroid cancer, thyroid gland tumor and normal tissues adjacent to tumors, and analyze clinical information. SPSS 13.0 statistical software was used for data analysis from chi square test, nonparametric test and Spearman correlation test. Test criterion for the P <0.05 was statistically significant.Results: In normal human thyroid tissues, a positive staining was observed mainly along the basal cell surface of the flattened follicular cells. In adenomas and Differentiated thyroid cancer tissues, a positive staining also was shown along the basal cell surface of the follicular cells. Besides, cytoplasmic staining was found. In anaplastic carcinoma tissues showed negative staining. There were positive rate of 87.3%, positive and strongly positive staining rate of 64.5% in 79 cases of thyroid cancer. There were positive rate of 100%, positive and strongly positive staining rate of 89.3% in 28 cases of thyroid adenoma. There were positive rate of 100%,positive and strongly positive staining rate of 96.5% in 28 cases of normal thyroid tissues adjacent to tumors. The staining intensity of the thyroid cancer, thyroid adenoma and normal thyroid tissue adjacent to tumors indicated significant in three group from Kruskal-Wallis H test. Multiple comparisons of staining intensity were carried out in thyroid cancer, thyroid adenoma and normal thyroid tissues adjacent to tumor from Wilcoxon test. Between the three pairwise differences in staining intensity of TSH receptor were significantly. That staining intensity of TSH receptor of the normal thyroid tissues adjacent to tumors was higher than thyroid adenoma, whereas the staining intensity of thyroid adenoma was higher than the thyroid carcinoma.According to the degree of differentiation, thyroid cancer can be divided into anaplastic thyroid carcinoma and differentiated thyroid cancer. Anaplastic thyroid carcinoma 5cases, weakly positive staining of 2 cases; whereas the positive of differentiated thyroid cancer was 90.5%. There were statistical differences between anaplastic and differentiated thyroid cancer from wilcoxon test, that the staining intensity of TSH receptor of the differentiated thyroid cancer was higher than the anaplastic thyroid cancer.We can observed differentiated thyroid cancer by TNM staging: the positive rate of stageⅠ(29 cases) was 93.1%; the positive rate of stageⅡ(23 cases) was 91.3%; the positive rate of stageⅢ(18 cases) was 88.9%; the positive rate of stageⅣ(4 cases) was 75%. It suggests Positive expression rate decreased gradually with the staging degree. Among of the four groups of TSH receptor expression level was no significant difference, we still can not believe that there was a correlation between thyroid carcinoma of the clinical stage and TSH receptor expression level. In addition, we also compared the lymph node metastases, tumor size, patients gender, age with expression level TSH receptor, there were no statistical significance. Expression lever of TSH receptor can not be considered with these factors.Conclusion:1 TSH receptor expression of thyroid tissue with differentiation degree will decrease. In normal thyroid tissues and benign tumor had a higher expression of TSH receptor; anaplastic thyroid cancer is weakly express; expression of differentiated thyroid cancer in between. 2 It varied from negative to positive in TSH receptor of differentiation thyroid cancer. This study not only provides a theoretical basis for suppression therapy, but also provides help for clinical guide therapy.3 Expression of TSH receptor in thyroid cancer may be indirect indicators of grade malignancy.