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PubMed | Peking University, Peiking Union Medical College Hospital, National Cancer Center Cancer Hospital and Peking Union Medical College
Type: | Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine | Year: 2016

Telomerase Reverse Transcriptase (TERT) promoter mutation has been reported to be associated with aggressive characteristics in differentiated thyroid cancer (DTC). This study examined the status of TERT promoter mutation in distant metastatic DTC (DM-DTC), and evaluated the correlation between TERT mutation and radioactive iodine-131(RAI) uptake, as well as that between TERT mutation and therapy response.TERT promoter and B-Raf proto-oncogene (BRAF) V600E mutation were retrospectively examined in primary tumors of 66 DM-DTC patients. Stimulated thyroglobulin (sTg) changes, RAI uptake status (avid or non-avid), and other imaging evidence were analyzed to evaluate therapy response. After a median follow-up of 46.5 months (interquartile range, 29.0 to 70.5 months), therapy response was classified as disease control and refractory.The prevalence of TERT mutations was 22.73% (15/66), of which C228T mutation was more prevalent (13/15) than C250T mutation (2/15). Rising sTg was noticed in 93.33% (14/15) of TERT mutation group. While in cases with both mutations negative, 78.12 % (25/32) presented with decreased sTg. TERT mutation closely correlated with poor RAI therapy response (p0.001), and all 15 patients were classified as refractory to RAI with a positive predictive value of 100% at the end point of follow-up. TERT mutation was associated with older mean age at diagnosis (p0.001), larger mean tumor diameter (P = 0.013), and more likelihood of both BRAF mutation coexistence (P = 0.044) and refractory to RAI (p0.001). In the 36 cases received imaging semi-quantitative analysis, it was found that TERT mutation significantly correlated with non-RAI-avidity, with a much lower mean tumor/background (T/B) ratio (obtained from post RAI therapy whole-body scanning) than TERT wild-type (p0.001). And DM-DTC patients with TERT mutation were more likely to lose RAI-avidity at initial RAI therapy than those with only BRAF mutation (8/8 vs 5/11, Fishers exact test, P = 0.018).TERT promoter mutation closely associates with non-RAI-avidity in DM-DTC, and when comparing with BRAF mutation, TERT mutation manifested a worse negative influence on RAI uptake. It could also be used as a predictive marker to early identify refractory to RAI.

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