免疫组化测定Midkine和核因子κB对甲状腺乳头状癌以及转移灶的诊断价值  

Immunohistochemical evaluation of midkine and nuclear factor-κB as markers for diagnosis and prediction of synchronous metastasis in papillary thyroid cancer

作　　者：孟召伟[1] 谭建[1] 张玉洁[2] 张桂芝[1] 章明放 何雅静[1] 田伟军[4] 贾强[1] 何庆[5] 朱梅[5] 李雪[1] 张建萍[1] 

机构地区：[1]天津医科大学总医院核医学科,300052 [2]天津医科大学总医院病理科,300052 [3]天津第一中心医院病理科 [4]天津医科大学总医院普外科,300052 [5]天津医科大学总医院内分泌科,300052

出　　处：《中华内分泌代谢杂志》2015年第7期581-586,共6页Chinese Journal of Endocrinology and Metabolism

基　　金：国家临床重点专科资助（资助天津医科大学总医院影像医学与核医学）

摘　　要：目的Midkine（MK）和核因子κB（NF—κB）在肿瘤发生过程中起着重要的作用，均被认为是新的恶性肿瘤生物标志物。本研究旨在探讨免疫组化方法测定MK和NF—κB对甲状腺乳头状癌（PTC）的诊断价值以及对PTC是否同时存在转移灶的判断价值。方法对76例PTC和70例结节性甲状腺肿（MNG）的术后病灶进行研究，PTC组进一步分为亚组1（16例，有转移灶）和亚组2（60例，无转移灶），汇总所有患者的临床资料、影像学资料、手术后^131I治疗情况、^131I扫描结果等。MK、NF—κB p65和Ki-67的免疫组化在石蜡包埋的术后病灶标本上进行、并对结果进行量化（得到免疫组化积分或阳性百分率），对各个参数采用受试者工作特性曲线（ROC）进行统计分析，确定参数的诊断灵敏度、特异度、准确度、阳性预测值和阴性预测值。提取病灶蛋白，对MK和NF—κB p65进行Western印迹，证实上述免疫组化结果。结果MK和NF—κB p65的免疫组化积分、以及Ki-67的阳性百分率，PTC组明显高于MNG组（均P〈0．01）：ROC结果显示三者具有良好诊断PTC的能力，诊断准确度分别为82．192％、80．137％和84．091％。PTC亚组1的上述3个参数显著高于亚组2（均P〈0．01）；ROC结果显示三者具有良好诊断PTC转移灶的能力，诊断准确度分别为82．895％、80．263％和76．316％。Western印迹结果显示MK和NF—κB p65的蛋白水平在PTC亚组1明显高于亚组2，二者均明显高于MNG（均P〈0．01）。结论MK和NF—κB的免疫组化可以用于PTC和MNG的鉴别诊断，并且可以判断PTC是否存在转移。Objective Midkine （MK） and nuclear factor-kappa B （NF-κB） play pivotal roles in tumorigenesis, which are considered as promising cancer biomarkers. The efficacy of MK and NF-κB as markers for diagnosis and prediction of synchronous metastasis in papillary thyroid cancer （PTC） was the aim of present investigation. Methods Seventy six cases of PTC and seventy eases of multi-nodular goiter （MNG） were retrieved. The PTC group was further divided into subgroup 1 （ 16 cases with synchronous metastasis） and subgroup 2 （60 cases without metastases）. A retrospective review of clinical information, radiological examinations,^131I treatments and post-^131 I-therapy scans were done. Immunohistochemistry of MK, NF-κB p65, and Ki-67 was performed on paraffin-embedded specimens and results were quantified. Diagnostic values of the parameters were conducted by receiver operating characteristic （ROC） curves. Diagnostic sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were determined. Protein levels of MK and NF-κB p65 were then confirmed by Western blot. Results Immunoreactivities of MK and NF-κB p65, and positive percentage of Ki-67 were significantly higher in PTC group than in MNG group （ all P〈0.01 ）. ROC showed good differential diagnostic capabilities of all three parameters with diagnostic accuracies of 82.192%, 80. 137%, and 84.091% respectively. Moreover, all three parameters were significantly higher in subgroup 1 than those in subgroup 2 （ all P〈 0. 01 ）. ROC showed good predicting efficacies in synchronous metastasis of all three parameters with diagnostic accuracies of 82. 895% , 80. 263% , and 76. 316% respectively. By one-way analysis of variance, Western blot showed that MK and NF-κB p65 protein levels in lesions from subgroup 1 were significantly higher than those from subgroup 2, both were significantly higher than lhose in MNG lesions （ P 〈0.01 ）. Conclusion MK and NF-κB immunohistochemistry can potentially be used

关 键 词：MIDKINE 核因子ΚB 甲状腺乳头状癌 结节性甲状腺肿 

分 类 号：R736.1[医药卫生—肿瘤] R730.4[医药卫生—临床医学]