Programmed Death-Ligand 1 Expression in Papillary Thyroid Cancer and Its Correlation with Clinicopathologic Factors and Recurrence.

BACKGROUND: Programmed death-ligand 1 (PD-L1) expression has been reported in several malignancies, but the expression of PD-L1 in papillary thyroid cancer (PTC) has been characterized rarely. The aim of this study was to assess the significance of PD-L1 expression and its associations with clinicopathologic factors and disease outcome in PTC. METHODS: Immunohistochemistry staining was conducted retrospectively to evaluate the expression of PD-L1 in a total of 260 PTC tumors and corresponding non-tumor tissues. The correlations between PD-L1 expressions with clinicopathologic features and recurrence-free survival (RFS) were analyzed. RESULTS: PD-L1 expression was positive in 52.3% (136/260) of PTC tumor tissues, which was significantly higher than in corresponding non-tumor thyroid tissues. In clinicopathologic analyses, this positive staining of PD-L1 was positively linked to multifocality (p = 0.001) and extrathyroidal extension (p = 0.001). In multivariate Cox regression analysis, positive PD-L1 expression in tumor tissue was significantly associated with worse RFS (hazard ratio 2.825 [confidence interval 1.149-6.943], p = 0.024). In subgroup analyses based on clinicopathologic factors, positive PD-L1 staining of tumor tissue was associated with worse RFS in males (p = 0.001), older patients (≥45 years; p = 0.001), and patients with a primary tumor size >4 cm (p = 0.002), multifocal tumors (p = 0.031), extrathyroidal extension (p = 0.012), and lymph node metastasis (p = 0.004). In contrast, positive PD-L1 staining predicted worse RFS in the subgroup of patients without Hashimoto's thyroiditis (p = 0.001) and treated with total thyroidectomy (p = 0.019). CONCLUSIONS: PD-L1 is important in determining aggressiveness of PTC and could predict the prognosis of patients. Therefore, inhibition of PD-L1 is suggested as a potential strategy for the treatment of advanced PTC with high expression of PD-L1.

Prognostic significance and optimal cutoff of age in medullary thyroid cancer.

Age has been found to correlate with the prognosis for medullary thyroid cancer (MTC). This study was conducted to investigate whether age can predict long-term unfavorable prognosis and evaluate its predictive accuracy associated with TNM staging, using data of patients diagnosed with MTC between 2000 and 2010 from Surveillance, Epidemiology and End Results database. The relationship between the patients' age at diagnosis and cancer-specific survival (CSS) was evaluated using multivariate Cox regression analysis. Age stratifications were combined into a nomogram model to predict the CSS of MTC. The X-tile program determined 49 and 69 as optimal age cutoff values for CSS. On multivariate analysis, independent factors for survival were age (50-69 years, HR 2.853, 95% CI 1.631-4.991; ≥70 years, HR 5.804, 95% CI 2.91-11.555), race (white, HR 0.344, 95% CI 0.188-0.630), T (T3/4, HR 3.931, 95% CI 2.093-7.381), N (N1a, HR 3.269, 95% CI 1.386-7.710) and M (M1, HR 3.998, 95% CI 2.419-6.606). The C-index for CSS prediction with TNM, age (cutoff of 45)/sex/race/TNM and age (cutoff of 49 and 69)/sex/race/TNM were 0.832 (95% CI 0.763-0.901), 0.863 (95% CI 0.799-0.928), and 0.876 (95% CI 0.817-0.935), respectively. Subgroup multivariate analyses also showed that age significantly increased the risk for CSS in females, non-Hispanic white patients, and those with stage IV MTC. In conclusion, CSS was independently associated with ages between 49 and 69 years, which might be applied for risk stratification in MTC patients.