BRAF, TERT and HLA-G Status in the Papillary Thyroid Carcinoma: A Clinicopathological Association Study

Abstract

As BRAF, TERT, HLA-G, and microRNAs have been individually associated with papillary thyroid carcinoma (PTC), we aimed to evaluate the individual and collaborative role of these markers in PTC in the same patient cohort. HLA-G and BRAF tumor expression was evaluated by immunohistochemistry. Using molecular methods, BRAF^V600E and <i>TERT</i> promoter mutations were evaluated in thyroid fine needle aspirates. MicroRNA tumor profiling was investigated using massively parallel sequencing. We observed strong HLA-G (67.96%) while BRAF (62.43%) staining was observed in PTC specimens. BRAF overexpression was associated with poor response to therapy. The BRAF^V600E (52.9%) and <i>TERT</i>^C228T (13%) mutations were associated with extrathyroidal extension, advanced-age, and advanced-stage cancer. The <i>TERT</i> rs2853669 CC+TC genotypes (38%) were overrepresented in metastatic tumors. Nine modulated microRNAs targeting the <i>BRAF, TERT,</i> and/or <i>HLA-G</i> genes were observed in PTC and involved with cancer-related signaling pathways. The markers were individually associated with PTC features, emphasizing the synergistic effect of BRAF^V600E and <i>TERT</i>^C228T; however, their collaborative role on PTC outcome was not fully demonstrated. The differentially expressed miRNAs targeting the <i>BRAF</i> and/or <i>HLA-G</i> genes may explain their increased expression in the tumor milieu.