The best predictors of persistence were tumour size and macroscopic lymph node metastasis; when the initial surgery is of quality, the recurrence depends more on tumour's biology aspects.
BackgroundNKX2.5 is a transcription factor transiently expressed during thyroid organogenesis. Recently, several works have pointed out the oncogenic role of NKX2.5 in a variety of tumors. We therefore hypothesized that NKX2.5 could also play a role in thyroid cancer.MethodsThe validation of NKX2.5 expression was assessed by immunohistochemistry analysis in a Brazilian case series of 10 papillary thyroid carcinoma (PTC) patients. Then, the long-term prognostic value of NKX2.5 and its correlation with clinicopathologic features of 51 PTC patients was evaluated in a cohort with 10-years follow-up (1990–1999). Besides, the effect of NKX2.5 overexpression on thyroid differentiation markers and function was also investigated in a non-tumor thyroid cell line (PCCL3).ResultsNKX2.5 was shown to be expressed in most PTC samples (8/10, case series; 27/51, cohort). Patients who had tumors expressing NKX2.5 showed lower rates of persistence/recurrence (p = 0.013). Overexpression of NKX2.5 in PCCL3 cells led to: 1) downregulation of thyroid differentiation markers (thyrotropin receptor, thyroperoxidase and sodium-iodide symporter); 2) reduced iodide uptake; 3) increased extracellular H2O2 generation, dual oxidase 1 mRNA levels and activity of DuOx1 promoter.ConclusionsIn summary, NKX2.5 is expressed in most PTC samples analyzed and its presence correlates to better prognosis of PTC. In vitro, NKX2.5 overexpression reduces the expression of thyroid differentiation markers and increases ROS production. Thus, our data suggests that NKX2.5 could play a role in thyroid carcinogenesis.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4399-1) contains supplementary material, which is available to authorized users.
Despite its indolent course, one-third of the papillary thyroid carcinoma (PTC) cases relapses, which directly impact on the quality of patients' lives. The molecular predictors of recurrence of PTC are poorly defined. We aimed at evaluating the long-term (10–20 years) prognostic value of aggressiveness markers in advanced PTC. To this end, immunohistochemistry for BRAFV600E, Estrogen receptor α, Progesterone receptor, Ki-67, and E-cadherin were performed in 53 primary advanced PTC from an up to 20 years follow-up patients from a well-characterized Brazilian cohort. Categorical data were summarized using frequencies and groups were compared using Chi-squared and Fisher's exact tests. The expressions of the aggressiveness markers were associated with clinical-pathological data using the single-covariate logistic regression analysis. The Kaplan-Meier method with the Log-rank and Peto tests was used to estimate the probability of PTC-free survival. Persistence and recurrence (active disease) were associated with age (≥55 years), tumor size (>2 cm), extrathyroidal extension, local aggressiveness, macroscopic lymph node metastasis, and TNM stage at initial treatment. The BRAFV600E mutation status was associated with extrathyroidal extension, local aggressiveness, and inversely associated with distant metastasis at initial treatment. All progesterone receptor-positive patients had active disease and displayed a shorter time of PTC-free survival than the negative ones using the Kaplan-Meir analysis (p = 0.001, Log Rank; p = 0.005, Peto). Loss of E-cadherin expression was associated with an increase in the probability of active disease (OR = 3.75). BRAFV600E could be useful as a biomarker of local aggressiveness, while PR positive and E-cadherin loss of expression could predict the recurrence of advanced PTC.
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