目的:检测甲状腺乳头状微小癌(PTMC)及其癌旁良性组织中细胞凋亡抑制因子存活素(survivin)、半乳糖凝集素-3(Gal-3)和甲状腺髓过氧化物酶(TPO)蛋白表达差异以及PTMC中鼠类肉瘤滤过性毒菌致癌同源体B1(BRAF)基因的突变,探讨survivin、Gal-3和TPO蛋白与BRAFV600E基因突变的关系。方法:采用免疫组织化学方法检测56例PTMC组织及其癌旁良性组织中survivin、Gal-3和TPO蛋白的表达情况;对聚合酶链式反应(PCR)扩增产物直接测序,分析BRAFV600E基因突变情况;survivin、Gal-3和TPO蛋白表达阳性率与BRAF基因突变率关系分析采用χ2检验方法。结果:PTMC癌组织中,survivin和Gal-3强阳性表达,而TPO不表达;癌旁良性组织中,survivin和Gal-3表达缺失,TPO正常表达;survivin、Gal-3和TPO在癌组织和其癌旁良性组织间的表达率比较差异均有统计学意义(均P〈0.001);BRAFV600E基因在PTMC中有32.1%(18/56)突变;BRAFV600E基因突变率和3种蛋白在PTMC组织中的表达率与淋巴结转移有关联(P=0.009,P=0.025,P=0.007,P=0.008),而与患者年龄和性别无关联(均P〉0.05);BRAFV600E基因突变与survivin、Gal-3、TPO蛋白表达均无关联(均P〉0.05)。结论:PTMC癌组织中,survivin和Gal-3表达升高、TPO表达降低和BRAFV600E基因突变可能在PTMC发生发展中起重要作用,survivin、Gal-3、TPO蛋白表达与BRAFV600E基因突变的检测,可为PTMC病情的判定、预后的转归提供有价值的信息。
Objective: To detect the expressions of survivin, galectin-3 and thyroid peroxidase in papillary thyroid microcarcinoma (PTMC) and cancer adjacent normal tissue to explore the clinical significant. The correlations between the expressions of survivin,Gal-3 and TPO with BRAF^V600E gene mutation in PTMC were analyzed. Methods: The expressions of survivin, Gal-3 and TPO were measured by immunohistoehemical ( IHC ) method in 56 cases of PTMC tissue and adjacent normal tissue ; BRAF^V600Emutation was detected by PCR amplification and subsequently sequencing. Chi square test was used to analyse the relation in the expression rates of survivin, Gal-3 and TPO and BRAF^V600E gene mutation. Results : The survivin and Gal-3 were strongly expressed but TPO was negatively expressed. The survivin and Gal-3 were negative in adjacent normal tissues but TPO was expressed. There were sig- nificant differences in the expression rates of survivin, Gal-3 and TPO between PTMC tissue and adjacent normal tissue (all P〈0. 001). The BRAF^V600E mutation rate (32. 1% ) and the expression rates of survivin, Gal-3 and TPO in PTMC tissue were found to be positively related to lymph node metastases (P = 0. 009, P = 0. 025, P = 0. 007, P = O. 008 ), and negatively related to gender and age ( all P〉0.05 ). There were no correlation was found between the expressions of survivin, Gal-3, TPO and the BRAF^V600E gene mutation in PTMC ( all P〉0.05 ). Conclusion: The strong expressions of survivin and Gal-3, the mild expression of TPO and BRAF mutation may be important in the development of PTMC, and the detection of BRAF^V600E gene mutation and the expressions of survivin,Gal-3 and TPO could be used to the judgment of pathogenetic condition and prognostic outcomes.