To 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).

Immunohistochemical 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.

(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.

CK19, 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.