肿瘤转移抑制基因KISS-1在甲状腺癌组织中表达和预后的研究

目的检测KISS-1蛋白、基质金属蛋白酶(MMP)-2、MMP-9及Ki67在甲状腺癌中的表达,探讨4者在甲状腺癌发生发展过程中的作用。方法采用免疫组织化学SP法检测10例正常甲状腺组织、12例结节性甲状腺肿,13例甲状腺腺瘤,68例甲状腺癌组织KISS-1蛋白、MMP-2、MMP-9及Ki-67的表达,分析4者在不同临床病理特征中表达的意义及它们之间的相关性。结果甲状腺癌组KISS-1蛋白阳性表达率(37%)明显低于正常甲状腺组织、结节性甲状腺肿和甲状腺腺瘤组(分别为100%、83%、62%,P<0.01),并且KISS-1蛋白低表达与甲状腺癌的临床分期和淋巴结转移有关(P<0.05),与甲状腺癌患者的年龄、病理类型无关(P>0.05)。甲状腺癌组和结节性甲状腺肿和甲状腺腺瘤组MMP-2阳性表达率(分别为78%,54%、67%)明显高于正常甲状腺组(10%,P<0.01),并且MMP-2高表达与甲状腺癌的临床分期和淋巴结转移有关(P<0.05),与甲状腺癌患者的年龄、病理学类型无关(P>0.05)。甲状腺癌组和结节性甲状腺肿和甲状腺腺瘤组MMP-9阳性表达率(分别为82%,69%、58%)明显高于正常甲状腺组(20%,P<0.01),并且MMP-9高表达与甲状腺癌的临床分期和淋巴结转移有关(P<0.05),与甲状腺癌患者的年龄、病理学类型无关(P>0.05)。甲状腺癌组Ki67阳性表达率(88%)明显高于正常甲状腺组和结节性甲状腺肿和甲状腺腺瘤组(10%、31%、42%;P<0.01),并且Ki67高表达与甲状腺癌的临床分期有关(P<0.05),与甲状腺癌患者的年龄、病理学类型和淋巴结转移无关(P>0.05)。结论 KISS-1蛋白、MMP-2、MMP-9及Ki-67与甲状腺癌的发生发展有关,联合检测4者的表达可能作为评估甲状腺癌预后和指导临床靶向治疗的重要指标。

The expression and prognosis of tumor metastasis suppressor gene KISS-1 in the tissues of thyroid cancer

Objective To detect the expressions of KISS-1 protein, MMP-2, MMP-9 and Ki-67 in thyroid cancer, and to explore the effects of these four proteins on occurrence and development of thyroid cancer. Methods Immunohistochemical SP method was used to detect the expression of KISS-1 protein, MMP-2, MMP-9 and Ki-67 in 10 cases of normal thyroid tissue, 12 cases of nodular goiter, 13 cases of thyroid adenoma and 68 cases of thyroid carcinoma tissues. Thereafter, the significance of expressions of 4 proteins was analyzed in different clinical pathological characteristics and their correlations. Results In thyroid cancer group, the positive expression rate of KISS-1 protein （37%） was significantly lower than that in normal thyroid tissues, nodular goiter and thyroid adenoma groups （100%, 83%, 62%, P0.01）. Moreover, the expression of KISS-1 protein was correlated with the clinical staging and lymphatic metastasis but no with the age, pathological type of patients with thyroid cancer （P0.05）. The positive rates of MMP-2 in thyroid cancer, nodular goiter and thyroid adenoma groups were respectively 78%, 54% and 67%, which were significantly higher than that in normal thyroid gland group （10%,P0.01）. Furthermore, the overexpression of MMP-2 had a correlation with clinical staging of thyroid cancer and lymphatic metastasis （P0.05） but not with the age and pathological type of the patients with thyroid cancer （P0.05）. The positive expression rates of MMP-9 in thyroid cancer, nodular goiter and thyroid adenoma groups were respectively 82%, 69% and 58%, which were obviously higher than that in normal thyroid gland group （20%, P0.01）. In addition, the overexpression of MMP-9 was correlated with the clinical staging of thyroid cancer and lymphatic metastasis but not with the age and pathological type （P0.05）. The positive rate of Ki-67 in thyroid cancer group （88%） was significantly higher than that in normal thyroid gland, nodular goiter and thyroid adenoma groups （10%, 31%, 42%; P0.01）. Moreover, the overexpression of Ki-67 was correlated with the clinical staging of thyroid cancer but not with the age, pathological type and lymphatic metastasis （P0.05）. The expression of KISS-1 protein was negatively correlated with the expressions of MMP-2 and MMP-9 in thyroid cancer （r =-0.399, P0.01）. Conclusion The expressions of KISS-1 protein, MMP-2, MMP-9 and Ki-67 were correlated with the occurrence and development of thyroid cancer. The combined detection of the expression of these four proteins might be used as the important indicators in evaluating prognosis of thyroid cancer and guiding clinical target treatment.