Clinical, pathological, biochemical and genomic characteristics of poorly differentiated thyroid cancer

This is a comprehensive study of one of the largest cohort of poorly differentiated thyroid carcinoma (PDTC) patients reported in the literature, diagnosed by criteria of proliferative grading and treated surgically at a tertiary care academic center, with or without adjuvant therapy. The main objectives were: to report on clinicopathological, biochemical and genomic characteristics of PDTC patients, to correlate those characteristics with outcome and to report on the patterns of treatment failure. PDTC patients presented with adverse clinicopathological characteristics of thyroid cancer: older age, male gender, local spread and tendency for distant spread. pT4a and M1 remained significant predictors of worse outcome on multivariate analysis. Undetectable Tg after initial treatment of PDTC patients can predict low risk of recurrence, nevertheless a close follow-up is needed due to heterogeneity of PDTC. Initial adequate surgery can achieve satisfactory locoregional control, however distant metastases represent the major cause of cause-specific deaths. By using ultra deep next-generation sequencing, important biomarkers for aggressive behavior of PDTC were identified. Comparison between fatal and nonfatal cases of PDTC revealed that fatal PDTC show a higher frequency of mutations in: TERT promoter, MED12, RBM10, BRAF, HRAS, TP53, ATM and EIF1AX. In addition chromosomal 1q gains are the most common arm level alterations in PDTC and those patients show worse survival rates. We anticipate that these insights into PDTC biology will contribute to the development of standardized clinical guidelines and development of effective targeted therapies in order to improve the outcomes in patients with PDTC.