The gene expression of GPER1 is low in fresh samples of papillary thyroid carcinoma (PTC), and in silico analysis.

Papillary thyroid cancer (PTC), whose incidence has been increasing in the last years, occurs more frequently in women. Experimental studies suggested that estrogen could be an important risk factor for the higher female incidence. In fact, it has been demonstrated that 17ß-estradiol (E2) could increase proliferation and dedifferentiation in thyroid follicular cells. Genomic estrogen responses are typically mediated through classical estrogen receptors, the α and ß isoforms, which have been described in normal and abnormal human thyroid tissue. Nevertheless, effects mediated through G protein estrogen receptor 1 (GPR30/GPER/GPER1), described in some thyroid cancer cell lines, could be partially responsible for the regulation of growth in normal cells. In this study, GPER1 gene and protein expression are described in non-malignant and in papillary thyroid cancer (PTC), as well as its association with clinical features of patients with PTC. The GPER1 expression was lower in PTC as compared to paired non-malignant thyroid tissues in fresh samples of PTC and in silico analysis of GEO and TCGA databases. In PTC cases of TCGA database, low GPER1 mRNA expression was independently associated with metastatic lymph nodes, female gender, and BRAF mutation. Besides, GPER1 mRNA levels were positively correlated with mRNA levels of thyroid differentiation genes. These results support the hypothesis that GPER1 have a role in PTC tumorigenesis and might be a potential target for its therapy. Further studies are needed to determine the functionality of these receptors in normal and diseased thyroid.

Thyroglobulin Antibodies as a Prognostic Factor in Papillary Thyroid Carcinoma Patients with Indeterminate Response After Initial Therapy.

The clinical outcome of papillary thyroid carcinoma (PTC) patients with an indeterminate response after initial therapy is reported to be intermediate, between incomplete and excellent responses. This study evaluated the outcomes of PTC patients with indeterminate response after initial therapy. It was further determined whether the indeterminate findings predicted outcomes more precisely. Patients were further classified into 3 groups based on risk of structural persistence/recurrence: Tg group: detectable thyroglobulin, negative antithyroglobulin antibody, regardless nonspecific imaging findings; TgAb group: positive antithyroglobulin antibody, regardless thyroglobulin levels and nonspecific imaging findings, and Image group: nonspecific findings on neck ultrasonography or faint uptake in the thyroid bed on whole-body scan, undetectable thyroglobulin and negative antithyroglobulin antibody. Sixty-six patients aged 44.1±12.7 years were studied, of whom 58 (87.9%) were females. All patients underwent total thyroidectomy, and 52 patients (78.8%) received radioiodine. After 5.7 years (P25-75 2.6-9.75 years) of follow-up, most patients (89.4%) were reclassified as having an excellent response or remained in the indeterminate response to therapy. Structural recurrence/persistence disease was detected in 7 (10.6%) patients. The persistence/recurrence rate in groups were as follow: Tg, 2.63%; TgAb, 31.25%; Image, 8.3% (p=0.007). The 10-years disease-free survival rate in the TgAb group was significantly reduced (p=0.022). Our results suggest that patients with PTC and indeterminate response due to positive serum antithyroglobulin antibody have more risk of development of structural disease. These findings suggest a more individualized follow-up strategy for patients with an indeterminate response.