The efficacy of chemokine C-X-C motif ligand 12 as a diagnostic marker for papillary thyroid carcinoma

Abstract

The incidence of thyroid cancer is increasing worldwide, with the most dramatic growth being the up to 25% annual increase observed over the last 10 years in Korea. Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer in Korea, and it is essential to develop methods for the accurate diagnosis of PTC to avoid unnecessary surgery. Chemokine C-X-C motif ligand 12 (CXCL12) has been reported to be associated with chemokine C-X-C motif receptor 4 (CXCR4) mediated activation of G-protein-coupled signaling molecules in various cancers. We aimed to study the efficacy of CXCL12 for the diagnosis of PTC. We prospectively collected 58 PTC samples from 2013 to 2015 and obtained 31 benign thyroid disease samples from the Korea Biobank of Jeju National University Hospital. Immunohistochemical and immunocytochemical staining for CXCL12 and B-type Raf kinase (BRAF) V600E mutant protein were performed on fine-needle aspiration (FNA) and tissue microarray (TMA). A BRAF V600E gene mutation study was also performed. The mean age of the subjects was 49.1±1.4 years and 88.5% were wemen. CXCL12 and BRAF were positive in 6.4% and 19.4% of cases of benign disease and 98.3% and 93.1% of PTCs, respectively. The sensitivity of CXCL12 was 93.1% in FNA and 98.3% in TMA, and that of BRAF was 62.1% in FNA and 93.1% in TMA. CXCL12 showed 90.3% specificity, 94.7% positive predictive value, 87.5% negative predictive value and 89.1% accuracy for diagnosis of PTC. Among the cases of atypia of undetermined significance (AUS), CXCL12 in FNA showed 100% sensitivity and 100% specificity compared with 62.5% sensitivity and 100% for BRAF. Strong CXCL12 expression (3+) was correlated with lymph node metastasis (p = 0.031), but not tumor size. In conclusion, CXCL12 in FNA and TMA may be an effective diagnostic marker for PTC and could facilitate its accurate diagnosis, especially in cases where the FNA is initially reported as AUS.