肝素结合细胞因子Midkine与甲状腺乳头状癌肿瘤生物学特征和BRAF突变的关系  

Expression of Midkine and Its Relationship with Clinicopathological Characteristics and BRAF Mutation in Papillary Thyroid Cancer

作　　者：宝荣[1] 王欣[2] 王佾[1] 关海霞[2] 

机构地区：[1]重庆市第九人民医院病理科,重庆400700 [2]中国医科大学附属第一医院内分泌科,内分泌研究所,沈阳110001

出　　处：《中国医科大学学报》2010年第7期518-520,528,共4页Journal of China Medical University

基　　金：国家自然科学基金资助项目(30801120);辽宁省创新团队课题基金资助项目(T2008204)

摘　　要：目的研究肝素结合因子Midkine(MK)在甲状腺乳头状癌(PTC)中的表达,探讨其表达与肿瘤生物学特征和BRAF突变的关系。方法采用免疫组化染色法检测100例PTC、30例甲状腺腺瘤和20例癌旁正常甲状腺组织中MK的表达,应用直接测序检测PTC中BRAF基因突变,分析PTC中MK的表达水平与肿瘤生物学特征及BRAF突变的关系。结果癌旁正常甲状腺组织中未检测到MK的表达,甲状腺腺瘤的MK表达率和平均表达评分分别为6.7%和0.07,PTC中MK的表达率和平均表达评分分别为87%和1.98。伴甲状腺腺外侵袭、淋巴结转移或恶性程度较高的Ⅲ/Ⅳ期PTC中MK表达呈强阳性,且其阳性率和平均染色评分均显著高于无侵袭、无转移或Ⅰ/Ⅱ期PTC(P<0.05)。癌旁正常甲状腺组织中未检测到BRAF突变,PTC中BRAF突变率为63%。BRAF突变的PTC中MK表达量显著高于野生型BRAF组(P<0.05)。结论 MK在PTC中表达增加,其表达量与PTC恶性程度及BRAF突变密切相关。Objective To detect the expression of Midkine（MK）in papillary thyroid cancer（PTC）,and to evaluate if the expression of MK correlates with clinicopathological characteristics and BRAF mutation in PTC.Methods The expression of MK in samples from 100 cases of PTC,30 cases of thyroid adenoma,and 20 cases of tumor-adjacent normal tissues was detected by immunohistochemistry.The BRAF mutation was detected by direct sequencing.The relationship between MK expression and the clinicopathological characteristics of PTC and BRAF mutation was analyzed.Results MK was not expressed in tumor-adjacent normal tissue.The positive expression rates and expression scores of MK were 6.7% and 0.07 in thyroid adenoma and 87% and 1.98 in PTC,respectively.The expression level of MK in PTC with extrathyroidal invasion and lymph node metastasis and in stages Ⅲ and Ⅳ PTC was significantly higher than that in PTC without extrathyroidal invasion and lymph node metastasis and in stages Ⅰ and Ⅱ PTC.The overall prevalence of BRAF mutation was 63% in PTC.The expression level of MK in PTC with BRAF mutation was significantly higher than that in PTC with wild-type BRAF gene.Conclusion The expression of MK is increased in PTC,and MK expression is closely correlated with the degree of malignancy of PTC and BRAF mutation.

关 键 词：肝素结合细胞因子 甲状腺乳头状癌 BRAF突变 

分 类 号：R736.1[医药卫生—肿瘤]