RESUMO
BACKGROUND: The inactivation of the tumor-suppressor homeodomain-only protein X (HOPX) usually involves promoter methylation in several cancer types. This study aimed to investigate the HOPX-ß mRNA expression and promoter methylation and their clinical relevance in differentiated thyroid cancer (DTC). PATIENTS AND METHODS: Clinicopathological data and paraffin-embedded thyroid tumor tissues from 21 patients with DTC and 6 with benign tumors (T) and their non-tumor parenchyma (NT) were investigated. Tumor cell lines (FTC238, FTC236 and WRO) were treated with demethylating agent. HOPX-ß mRNA expression was assessed by qRT-PCR and methylation status by Q-MSP. Thyroid cancer data from Cancer Genome Atlas (TCGA) was also collected. RESULTS: HOPX-ß mRNA re-expression in two cell lines treated with demethylating agent was observed concomitantly with reduced promoter methylation. Reduced mRNA expression in T group compared to their NT was observed, and reduced protein expression in T compared to NT was observed in three cases. Low mRNA expression with high methylation status was detected in 6/14 DTC samples. High methylation status was associated with older age at diagnosis, recurrent or progressive disease and with the presence of new neoplasm event post initial therapy while hyper-methylation correlated with worse overall survival, worse disease-free status and older age. CONCLUSION: A moderate coupling of downregulation of HOPX-ß mRNA expression in DTC followed by high HOPX-ß promoter methylation was observed however; high HOPX promoter methylation status was associated with the worse prognosis of DTC patients.
RESUMO
BACKGROUND: Some studies have demonstrated a correlation between the presence of a BRAF mutation and aggressive characteristics, including lymph node metastasis in papillary thyroid carcinoma (PTC). Prophylactic central neck dissection (CND) has been proposed for treatment of PTC. Given the potential complications of CND, we undertook a prospective study to determine the correlation between the BRAF mutation and lymph node metastasis. METHODS: A total of 51 patients with PTC underwent total thyroidectomy and routine prophylactic CND. All patients were tested for the BRAF mutation. RESULTS: Positive lymph nodes were found in 54.9% of patients. The BRAF mutation was found in 15 patients (29%). BRAF was not correlated with lymph node metastases. Lymph node metastases were correlated with multifocality (p=0.005) and angiolymphatic invasion (p=0.003) in univariate analysis. Age was also significant in multivariate analysis. CONCLUSIONS: Testing for the BRAF mutation does not help in deciding whether or not to perform CND.