细胞角蛋白19、半乳糖凝集素3、HBME-1和BRAF V600E表达在甲状腺结节的临床应用价值

目的探讨甲状腺结节患者中细胞角蛋白19（CK19）、半乳糖凝集素3（Galectin-3）、HBME-1、BRAF V600E的表达水平，从而分析4种分子标志物在鉴别甲状腺结节良恶性和甲状腺乳头状癌（PTC）的临床应用价值。 方法用免疫组织化学法检测746例甲状腺恶性结节（恶性组）及287例甲状腺良性结节（良性组）患者术后病理标本中CK19、HBME-1、Galectin-3和BRAF V600E的表达，评估各标志物单独及联合检测对PTC的诊断效能及意义。 结果（1）CK19、HBME-1、Galectin-3及BRAF V600E在恶性组的表达阳性率明显高于良性组（P<0.05）。（2）单独诊断PTC时，Galectin-3敏感度和准确性最高，BRAF V600E特异度最高；CK19+HBME-1+Galectin-3联合检测敏感度和准确性最高，分别为93.60%、94.49%。（3）CK19、Galectin-3、HBME-1及BRAF V600E表达阳性率均与PTC合并甲状腺良性病变呈正相关（r_s>0，P<0.05）。CK19、Galectin-3及BRAF V600E表达与病灶数目相关（P<0.05），且Galectin-3、BRAF V600E表达与微小癌病灶大小呈负相关（r_s<0，P<0.05）。BRAF V600E表达与淋巴结转移、促甲状腺激素水平相关（P<0.05）。（4）与单纯PTC比较，合并良性病变的PTC不易发生淋巴结转移，合并桥本甲状腺炎的PTC多灶癌所占比例较高。 结论CK19、Galectin-3、HBME-1、BRAF V600E是甲状腺良恶性结节鉴别诊断重要的辅助指标，也是诊断PTC的肿瘤标志物，其中Galectin-3诊断效能最高，CK19、Galectin-3、HBME-1联合检测可提高PTC的诊断准确性。

Clinical value of CK19, HBME-1, Galectin-3 and BRAF V600E in thyroid nodules

ObjectiveTo investigate the expression levels of Cytokeratin 19 (CK19), Galectin-3, HBME-1, and BRAF V600E in patients with thyroid nodules, so as to analyze the clinical application value of four molecular markers in the differential diagnosis of benign and malignant thyroid nodules and papillary thyroid carcinoma (PTC). MethodsImmunohistochemical method was used to detect the expressions of CK19, HBME-1, Galectin-3 and BRAF V600E in specimens of 746 patients with malignant thyroid nodules (malignant group) and 287 patients with benign thyroid nodules (benign group), so as to evaluate the diagnostic value and significance of each marker and its combined detection in thyroid papillary carcinoma. Results(1) The positive rates of CK19, HBME-1, Galectin-3 and BRAF V600E in malignant group were significantly higher than those in benign group (P<0.05). (2) When diagnosing PTC alone, Galectin-3 had the highest sensitivity and accuracy, BRAF V600E had the highest specificity; the combined detection of CK19 + HBME-1 + Galectin-3 had the highest sensitivity and accuracy, which were 93.60% and 94.49% respectively. (3) The positive rate of expression of CK19, Galectin-3, HBME-1 and BRAF V600E were positively correlated with benign thyroid lesions (r_s>0, P<0.05) in PTC patients. The expressions of CK19, Galectin-3 and BRAF V600E were correlated with the number of lesions (P<0.05), and the expressions of Galectin-3 and BRAF V600E were negatively correlated with the size of microcarcinoma (r_s<0, P<0.05). The expression of BRAF V600E was correlated with lymph node metastasis and TSH (P<0.05). (4) Compared with PTC alone, PTC with benign lesions was less likely to have lymph node metastasis, and the proportion of multifocal carcinoma was higher in PTC patients with Hashimoto’s thyroiditis. ConclusionsCK19, HBME-1, Galectin-3 and BRAF V600E are important auxiliary indexes for differential diagnosis of benign and malignant thyroid nodules, and also important markers for the diagnosis of PTC. Galectin-3 has the highest diagnostic efficiency. The combined detection of CK19, Galectin-3 and HBME-1 can improve the diagnostic accuracy of PTC.