TERT Promoter Mutations Were Not Found in Papillary Thyroid Microcarcinomas That Showed Disease Progression on Active Surveillance

Abstract Papillary thyroid carcinoma (PTC) generally has an indolent course, and non-operative management is acknowledged for papillary thyroid microcarcinoma (PTMC). However, some PTMCs progress and we cannot predict future progression at their presentation. BRAF and TERT promoter mutations were recently reported to be associated with poor outcomes of PTC. Here we sought to determine whether these mutations are associated with the progression of PTMCs, toward the goal of predicting progression/nonprogression. From May 1995 to December 2012 at Kuma Hospital, 1,252 patients with low-risk PTMC chose active surveillance, and 188 of them underwent a conversion surgery later for various reasons. We selected the following three groups of patients for study. The Non-progressing group: 11 patients whose tumors did not progress for >5 years; the Size-increase group: 10 patients whose tumors increased by ≥4 mm in size, and the LN Metastasis group: five patients who showed the appearance of novel lymph node metastasis. We analyzed the BRAF and TERT promoter mutation statuses of the primary lesions of these patients' surgical specimens. The BRAF V600E mutation was detected in 64% of the Non-progressing group, 70% of the Size-increase group and 80% of the LN Metastasis group. The TERT promoter mutations (C228T and C250T) were not detected in any groups. BRAF mutation was not associated with tumor progression of low-risk PTMCs, and TERT promoter mutations were not detected regardless of the progression of the disease. These mutational analyses in PTMCs are unlikely to be useful for predicting their progression.