RESUMEN
Locally invasive papillary thyroid carcinoma (PTC) protrudes beyond the thyroid capsule and invades local structures. Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are implicated in local invasion and metastasis in PTC. The aim of our study was to determine expression levels of MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2 in tissue specimens of invasive and non-invasive PTC. Our hypothesis was that expression levels of these biomarkers correlate with the development of locally invasive PTC. In our single-center study we retrospectively investigated MMP and TIMP expression levels in 50 samples of thyroid tissue diagnosed as locally invasive papillary carcinoma (study group) and 30 samples of thyroid tissue diagnosed as non-invasive, non-metastatic papillary carcinoma (control group). Tissue specimens were immunohistochemically stained with primary monoclonal antibodies against MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2. When correlating expression levels of MMPs and TIMPs in thyroid tissue, statistically significant differences were found for MMP-1 and TIMP-1 expression (p < 0.001; Mann−Whitney U test) with the highest levels of expression in the invasive PTC group. Although expression of MMP-9 and TIMP-2 was higher in invasive PTC, the differences were not statistically significant. Elevated expression of MMP-1 and TIMP-1 in tumor tissue can predict invasiveness for PTC.
RESUMEN
The early-stage diagnosis of papillary thyroid cancer (PTC) has significantly increased in incidence worldwide without any beneficial impact on survival. In order to improve the risk assessment in PTC, we have conducted a retrospective study in which we analyzed the BRAF V600E mutation and CPSF2 protein expression as prognostic markers on archival tissue samples of 49 patients without (control group) and 97 patients with (study group) PTC metastases in the cervical lymph nodes at the time of initial diagnosis. Our aim was to correlate the BRAF V600E mutation and the expression of CPSF2 protein with the clinical and pathological features of PTC. The expression of CPSF2 protein was evaluated via immunohistochemistry and graded semi-quantitatively. The presence of the BRAF V600E mutation was determined via real-time polymerase chain reac-tion (PCR). CPSF2 protein < 3+ intensity expression was correlated with more frequent recurrences (Fisher-Freeman-Halton exact test; p = 0.010; 95% CI: 1.26−22.03), and patients who presented with the BRAF V600E mutation and CPSF2 protein expression < 3+ intensity had shorter disease-free survival (log-rank test; 105.0 months vs. 146.6 months; p < 0.001; HR 8.32, 95% CI: 2.91−23.83), whereas patients with PTC who had CPSF2 expression 3+ had longer disease-free survival in correlation with other lower intensity expressions of CPSF2 protein (log-rank test; 139.7 months vs. 129.6 months; p = 0.008). The multivariate analysis showed that younger patients with CPSF2 protein expression <3+ and the BRAF V600E mutation are at an increased risk for recurrence and require more intensive monitoring (Cox proportional hazards regression model; X2 = 17.5, df = 10, p = 0.025). Our results correlate the BRAF V600E mutation and CPSF2 protein expression with recurrence and disease-free survival as relevant prognostic factors for PTC.
RESUMEN
OBJECTIVE: To investigate possible metastasis predictors for neck sublevel IIb in papillary thyroid carcinoma (PTC) with lateral neck metastasis and to determine the reliability of preoperative ultrasound-guided fine-needle aspiration biopsy (FNAB) as a method of detecting positive lymph nodes in sublevel IIa in comparison with the finding of definitive pathohistological analysis. DESIGN: Prospective study with patients with proven lateral neck metastases from PTC at the time of initial diagnosis. All patients had total thyroidectomy, central neck dissection (level VI) and selective neck dissection (levels II-V). Potential predictive factors for the occurrence of metastasis in sublevel IIb were analysed. Sensitivity and specificity tests were used to determine the reliability of preoperative ultrasound-guided FNAB. Patients were monitored for recurrence for at least ten years. SETTING: Single-centre study. PARTICIPANTS: Study included 53 patients with proven lateral neck metastases from PTC at the time of initial diagnosis. RESULTS: Predictive factors for the occurrence of metastasis in sublevel IIb that have reached statistical significance are positive sublevel IIa, number of positive lymph nodes and positive levels IIa + III + IV + V. None of the patients who fulfilled predefined criterion for minimum 10-year follow-up had local recurrence in operated lateral levels. CONCLUSION: Highest clinical significance has positivity of sublevel IIa. Therefore, it is necessary to prove or exclude metastasis in sublevel IIa, preoperatively or intraoperatively, to decide whether to include sublevel IIb in dissection. Preoperative ultrasound-guided FNAB is a reliable method for the detection of positive lymph nodes in sublevel IIa in comparison with the definitive histopathological analysis.