The Significance Of The Expression Of STIP1, EMA And ER-α In Papillary Thyroid Carcinoma

Objective: To detect the different expression of Stress induced phosphoprotein1(STIP1), Epithelial membrane antigen(EMA) and Estrogen receptor-α(ER-α) in normal thyroid tissue, Hashimoto’s thyroiditis tissue nearby carcinoma, and papillary thyroid carcinoma tissue with or without lymph node metastasis, and analyze the correlation between the expression of these three proteins in papillary thyroid carcinoma and clinical pathological characteristics, finally, to provide evidences for the pathogenesis of papillary thyroid carcinoma.Methods: Collecting 54 thyroid tissue paraffin sections of inpatients with papillary thyroid carcinoma in Tangshan Gongren Hospital from January 2013 to December 2014. 15 of them comorbided with Hashimoto’s thyroiditis(3 sections without atypical Hashimoto’s thyroiditis were excluded), 18 of them comorbided with Lymph node metastasis(4 sections without atypical Lymph node metastasis were excluded), 10 paraffin sections from normal thyroid tissue nearby papillary thyroid carcinoma were served as control. Using Immunohistochemisty(PV) to detect the differrent expression of STIP1, EMA and ER-α in normal thyroid tissue, Hashimoto’s thyroiditis tissue nearby carcinoma, papillary thyroid carcinoma with or without lymph node metastasis; Applying SPSS14.0 to do the statistical analysis. Fisher test or χ2 test was used to compare the measurement data, and the relationship between the expression of these three proteins in papillary thyroid carcinoma and clinical pathological characteristics, such as sex, age, range of the lesions of carcinoma(include bilateral lobe or unilateral lobe), the number of lesions(include single focus, double focus or more), with or without capsule invasion, with or without lymph node metastasis, with or without Hashimoto’s thyroiditis or nodular goiter, TG-Ab(thyroglobulin antibody), TPO-Ab(thyroid peroxidase antibody). Spearman rank correlation was used to analyze the relationship of the three proteins.Rseults:1 The expression of STIP1 in normal thyroid tissue, Hashimoto’s thyroiditis tissue nearby carcinoma, papillary thyroid carcinoma with or without lymph node metastasis.The positive expression rates of STIP1 in normal thyroid tissue, Hashimoto’s thyroiditis tissue nearby carcinoma, and papillary thyroid carcinoma with or without lymph node metastasis were 10%(1/10), 8.3%(1/12), 55.6%(30/54) and 78.6%(11/14), respectively. The expression of STIP1 in papillary thyroid carcinoma(χ2=10.971, P=0.001) and lymph node metastasis(χ2=5.306, P=0.021) were both higher than that of normal thyroid tissue. Moreover, the expression of STIP1 in papillary thyroid carcinoma(χ2=12.82, P<0.001) and lymph node metastasis(χ2=8.790, P=0.003) were both higher than that of Hashimoto’s thyroiditis tissue nearby carcinoma group. However, there was no diffrence in the expression of STIP1 in papillary thyroid carcinoma with and without lymph node metastasis groups(χ2=2.460, P=0.117).The positive expression rates of STIP1 in papillary thyroid carcinoma with lymph node metastasis was higher than that of papillary thyroid carcinoma without lymph node metastasis group(χ2=5.400, P=0.020). Moreover, The expression of STIP1 in papillary thyroid carcinoma without lymph node metastasis was not correlated with sex, age, range of the lesions of carcinoma, the number of lesions, with or without capsule invasion, with or without Hashimoto’s thyroiditis or nodular goiter, TG-Ab, TPO-Ab(all P>0.05).2 The expression of EMA in normal thyroid tissue, Hashimoto’s thyroiditis tissue nearby carcinoma, papillary thyroid carcinoma with or without lymph node metastasis.The expression of EMA were expressed in the cytoplasm and the inner cavity edge of cell membrane.The positive rate of EMA protein expression were analyzed within the cytoplasm and in the cell membrane/cavity edge.The positive expression rates of EMA within the cytoplasm in normal thyroid tissue, Hashimoto’s thyroiditis tissue nearby carcinoma, and papillary thyroid carcinoma with or without lymph node metastasis were 80%(8/10), 25%(3/12), 64.8%(35/54) and 35.7%(5/14), respectively. The expression of EMA in Hashimoto’s thyroiditis tissue nearby carcinoma(χ2=6.600, P=0.01) were lower than that of normal thyroid tissue. The expression of EMA in papillary thyroid carcinoma without lymph node metastasis group(χ2=6.372, P=0.012) was higher than that of Hashimoto’s thyroiditis tissue nearby carcinoma and papillary thyroid carcinoma with lymph node metastasis group.However,compared with normal thyroid tissue,the expression of EMA in papillary thyroid carcinoma with lymph node metastasis show a trend of lowing down(χ2= 0.328,P=0.567).There were no diffrence in the expression of EMA in papillary thyroid carcinoma without lymph node metastasis(χ2= 2.997,P =0.083)groups compared with normal thyroid tissue.The expression of EMA within the cytoplasm in papillary thyroid carcinoma without lymph node metastasis was associated with range of the lesions of carcinoma. The expression of EMA was highly expressed(χ2= 6.102,P=0.014) When the maximum diameter of the tumor was greater than or equal to 1cm.However, The expression of EMA was not associated with sex, age, the number of lesions, location,with or without capsule invasion, with or without Hashimoto’s thyroiditis or nodular goiter, TG-Ab, TPO-Ab(all P>0.05).The positive expression rates of EMA in the cell membrane/cavity edge of normal thyroid tissue, Hashimoto’s thyroiditis tissue nearby carcinoma, and papillary thyroid carcinoma with or without lymph node metastasis were 10%(1/10), 100%(12/12), 44.4%(24/54) and 64.3%(9/14), respectively. The expression of EMA in Hashimoto’s thyroiditis tissue nearby carcinoma(χ2=14.743, P=0.000) and papillary thyroid carcinoma with lymph node metastasis(χ2= 5.016, P =0.025) were both higher than that of normal thyroid tissue.Moreover, the expression of EMA in Hashimoto’s thyroiditis tissue nearby carcinoma(χ2=12.222, P=0.000) was higher than that of papillary thyroid carcinoma without lymph node metastasis group. However, there were no diffrence in the expression of EMA in Hashimoto’s thyroiditis tissue nearby carcinoma(χ2=3.256, P=0.071)and papillary thyroid carcinoma without lymph node metastasis(χ2= 1.752, P=0.186)groups with papillary thyroid carcinoma with lymph node metastasis. Furthermore, there was no diffrence between the expression of EMA in normal thyroid tissue and papillary thyroid carcinoma without lymph node metastasis(χ2= 2.883, P= 0.090).The expression of EMA in papillary thyroid carcinoma without lymph node metastasis was not associated with sex, age, range of the lesions of carcinoma, the number of lesions, with or without capsule invasion, with or without Hashimoto’s thyroiditis or nodular goiter, TG-Ab, TPO-Ab(all P>0.05).The expression of ER-α in normal thyroid tissue, Hashimoto’s thyroiditis tissue nearby carcinoma, papillary thyroid carcinoma with or without lymph node metastasis.The positive expression rates of ER-α in normal thyroid tissue, Hashimoto’s thyroiditis tissue nearby carcinoma, and papillary thyroid carcinoma with or without lymph node metastasis were 0%(0/10), 0%(0/12), 44.4%(24/54) and 42.9%(6/14), respectively. The expression of ER-α in papillary thyroid carcinoma without lymph node metastasis(χ2=5.431, P= 0.021) was higher than that of normal thyroid tissue.However, there was no diffrence in the expression of ER-α in Hashimoto’s thyroiditis tissue nearby carcinoma( fisher’s, P=1.000) and papillary thyroid carcinoma with lymph node metastasis(χ2=3.657, P=0.056). Moreover, the expression of ER-α in papillary thyroid carcinoma with(χ2=4.489, P=0.034) or without(χ2=6.570, P=0.010) lymph node metastasis were higher than that of Hashimoto’s thyroiditis tissue nearby carcinoma group. However, there was no diffrence in the expression of ER-α in papillary thyroid carcinoma with and without lymph node metastasis groups(χ2=0.011,P=0.915).The expression of ER-α in papillary thyroid carcinoma without lymph node metastasis was associated with sex(χ2=6.615, P=0.010), with or without nodular goiter(χ2=5.574,P=0.018), TG-Ab(χ2=5.310,P=0.021). The expression of ER-α was higher when patients with nodular goiter or the gender is female, but was lower expressed when TG-Ab increasing. The expression of ER-α was not associated with age, range of the lesions of carcinoma, the number of lesions, with or without capsule invasion, with or without Hashimoto’s thyroiditis or lymph node metastasis, TPO-Ab(all P>0.05).4 The correlation among STIP1, EMA and ER-α.The expression of STIP1 was postively correlated with that of ER-α(r=0.313, P=0.021). However, there was no correlation between the expression of STIP1 and EMA(r=0.025, P=0.858), as well as that of ER-α and EMA(r=0.035, P =0.803).Conclusions:1 STIP1 and ER-α were higher expressed in papillary thyroid carcinoma, which may play an important role in the occurrence of papillary thyroid carcinoma.2 STIP1 was higher expressed in papillary thyroid carcinoma with lymph node metastasis, which can served as a predictor to predict lymph node metastasis.3 The expression of EMA on membrane / cavity margin can be used as early warning index which can indicates the inversion Hashimoto’s thyroiditis into thyroid papillary carcinoma. The expression of EMA in the cytoplasm can be used as one of the auxiliary index screening thyroid microcarcinoma.4 ER-α was higher expressed in papillary thyroid carcinoma when female patients’ age greater than or equal to 45 years old. Expression of estrogen receptor in papillary thyroid carcinoma may promote the occurrence of papillary thyroid carcinoma in older women.5 ER-α was lower expressed in papillary thyroid carcinoma when patients with Hashimoto’s thyroiditis. It was shown that ER-α is related to the occurrence of thyroid carcinoma, and thenodular goiter become carcinomatous change.6 The positive expression of STIP1 and ER-α in papillary thyroid carcinoma indicates a synergistic effects between them. Combined detection can offer help for the prediction of the biological behavior of the tumor and the prognosis of the patients.