甲状腺组织中COX-2、MMP-9、VEGF和RET的检测及其在甲状腺乳头状癌早期诊断中的意义

Detection of COX-2,MMP-9,VEGF and RET in thyroid tissues and significances in primary diagnosis of papillary thyroid carcinoma

目的:探讨环氧化酶-2(COX-2)、基质金属蛋白酶-9(MMP-9)、血管内皮生长因子(VEGF)和转染重排基因(RET)在甲状腺乳头状癌组织中的表达及对早期诊断的意义。方法:免疫组织化学法检测COX-2、MMP-9、VEGF和RET在甲状腺乳头状癌、甲状腺腺瘤、结节性甲状腺肿及正常甲状腺组织的表达情况,探讨几种基因用于诊断甲状腺乳头状癌的敏感性与特异性,以及四者之间的相关性,筛选出早期诊断甲状腺乳头状癌及判定是否有淋巴结转移的最敏感指标。结果:COX-2、MMP-9、VEGF和RET在甲状腺乳头状癌组织中的表达明显高于甲状腺良性病变组织,并与年龄、肿瘤直径、包膜完整性、临床分期有关(P<0.05);COX-2和MMP-9在甲状腺瘤组织的表达高于结节性甲状腺肿组织,差异有统计学意义(P<0.05),COX-2表达与淋巴结转移有关(P<0.05),四者均与性别无明显关系(P>0.05)。经筛选发现检测MMP-9是诊断早期甲状腺癌的敏感指标,其敏感性为90.9%,特异性为90.0%;COX-2可作为判定是否早期有淋巴结转移的敏感指标,其敏感性为77.8%,特异性为66.7%。结论:联合检测COX-2和MMP-9可作为甲状腺乳头状癌术前诊断和判定有无淋巴结转移的最敏感生物学指标。

Objective To study the expressions of cyclooxegenase-2（COX-2）,matrix metalloproteinases-9（MMP-9）,vascular endothelial growth factor（VEGF）,transfection rearrangerment gene（RET） in papillary thyroid carcinoma and significances in primary diagnosis.Methods The expressions of COX-2,MMP-9,VEGF and RET were detected in papillary thyroid carcinoma,thyroid adenoma,nodular goiter and normal thyroid tissues by immunohistochemical method.The diagnostic sensitivities and specificities of these genes in thyroid papillary carcinoma were discussed as well as the relativities between them.Finally,the most sensitive index of papillary thyroid carcinoma’s primary diagnosis and the assessment of lymph node metastasis was selected.Results The expressions of COX-2,MMP-9,VEGF and RET in papillary thyroid carcinoma group were obviously higher than those in thyroid benign tumors,which presented an intimate relationship with age,tumor size,membrane integrality and clinical stage（P〈0.05）,the expressions of COX-2 and MMP-9 in thyroid adenoma were higher than those in nodular goiter（P〈0.05）,the expression of COX-2 was correlated to lymph node metastasis（P〈0.05）,but all of them were negatively correlated to patient gender（P〉 0.05）.MMP-9 was regarded as a sensitive marker of diagnosis for early thyroid carcinoma by gene filtration,the sensitivity was 90.9% and the specificity was 90.0%.COX-2 could work as a marker to evaluate lymph node metastasis,the sensitivity was 77.8% and the specificity was 66.7%.Conclusion Combined detection of COX-2 and MMP-9 can be used as the most sensitive biological index in preoperative diagnosis of papillary thyroid carcinoma and assessment of lymph node metastasis.