TERT Promoter Mutation and Extent of Thyroidectomy in Patients with 1–4 cm Intrathyroidal Papillary Carcinoma

Abstract

There are concerns regarding overtreatment in papillary thyroid carcinoma (PTC). BRAF V600E and TERT promoter mutations play important roles in the development of PTC. However, initial surgical approaches for PTC based on genetic characteristics remain unclear. The present study aimed to identify genetic mutations as predictors of prognosis and to establish proper indications for lobectomy (LT) in patients with 1–4 cm intrathyroidal PTC. Prospectively accumulated data from 685 consecutive patients with PTC who underwent primary thyroid surgery at the Cancer Institute Hospital, Tokyo, Japan, between 2001 and 2012 were retrospectively reviewed. Of the 685 patients examined, 538 (78.5%) had BRAF V600E mutation and 133 (19.4%) had TERT promoter mutations. Patients with TERT promoter mutations displayed significantly worse outcomes than those without mutations (10-year cause-specific survival (CSS): 73.7% vs. 98.1%, p < 0.001; 10-year disease-free survival (DFS): 53.7% vs. 93.3%, p < 0.001). As for extent of thyroidectomy among TERT mutation-negative patients with 1–4 cm intrathyroidal PTC, patients who underwent LT showed no significant differences in 10-year CSS and 10-year DFS compared to patients who had total thyroidectomy (TT) under propensity score-matching. Avoiding TT for those patients indicates a possible pathway to prevent overtreatment and reduce postoperative complications.

High prevalence of TERT aberrations in myxoid liposarcoma: TERT reactivation may play a crucial role in tumorigenesis

“…For detection of TERT p hotspot mutations, C228T and C250T, we performed genomic PCR and Sanger sequencing as described previously 36 . Briefly, PCR was performed using PrimeSTAR ® GXL DNA polymerase (TaKaRa Bio).…”

Correlation between low expression of protein disulfide isomerase A3 and lymph node metastasis in papillary thyroid carcinoma and poor prognosis: a clinicopathological study of 1,139 cases with long-term follow-up

“…That is, patients with distant metastasis and older patients (≥50 years) with massive extrathyroidal invasion or large lymph node metastasis (LNM) (maximal diameter, ≥3 cm) were defined as high risk and all other patients were classified as low risk. According to the risk adapted management treatment approach, we provided treatment options as described in previous reports [4]. Briefly, we basically conducted lobectomy for patients with unilateral low-risk PTC.…”

“…Expression of PDIA3 was evaluated by immunohistochemistry of tissue microarrays (TMAs). We constructed TMA as previously described [4]. In brief, for each tumor, the experienced, boarded pathologists selected one-to several representative histological areas for tissue microarray.…”

“…Although PTC generally has an indolent and slow, progressive behavior, 5-10% of PTC patients experience a more aggressive clinical course, characterized by recurrent disease and early metastases, and resistance to radioactive iodine, resulting in increased mortality [2]. Aggressive clinicopathologic features of PTC such as large tumor size, multifocality, massive extrathyroidal extension, lymph vascular invasion, large or extranodal invasive lymph node metastasis (LNM), distant metastasis, histological subtypes, and TERT promoter mutation have been reported [3][4][5][6]. Despite these facts, biomarkers to identify aggressive types of PTC are limited, illustrating the need to establish reliable novel biomarkers.…”

Clinical Application of TERT Promoter Mutations in Urothelial Carcinoma

“…Although the C228T and C250T hotspot mutations generate identical binding motifs for the transcription factors, there seems to be differences between these two mutations. We selected previous reports with a large number of cases or with seminal initial significance and analyzed the association of frequency of TERT C228T mutation in entire TERT promoter mutation and that of TERT promoter mutation in various types of tumor specimens [melanoma (21,22,(24)(25)(26)(27)(28), glioblastoma (29)(30)(31)(32)(33)(34)(35), HCC (23,(36)(37)(38)(39)(40)(41), papillary thyroid carcinoma (42)(43)(44)(45)(46)(47)(48), UBC (23,(49)(50)(51)(52)(53)(54)(55)(56)(57)(58), and UTUC (23, 59)] (Figure 1). The size of the circles indicated the number of samples analyzed in each study.…”