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Context A dynamic risk stratification with modified initial estimated risk based on response to therapy and disease course is one of the crucial changes adopted recently by the American Thyroid Association (ATA). This approach focuses on an individualized risk-adapted approach to the management of differentiated thyroid cancer. The BRAF V600E mutation is the most common genetic alteration in papillary thyroid cancer (PTC). However, the prognostic value of this mutation remains unclear. Objective The aim of this study was to examine the relation between the BRAF V600E status in PTC and all ATA response to therapy categories, as well as the recurrence and persistence of both biochemical and structural disease. Participants Unselected PTC cases with known BRAF status diagnosed from 2000–2013 and actively monitored at one institution (n=723) were reviewed retrospectively. Main Outcome Measures The association between the BRAF V600E mutation and clinicopathological characteristics, ATA 2015 response-to-therapy category, recurrence after a period of no evidence of disease (NED), and persistent biochemical or structural disease were analyzed. Results BRAF V600E was found in 65.7% (475/723) of PTC cases. Although BRAF mutation status correlated significantly with certain clinicopathological prognostic factors, there was no correlation with any of the response to therapy categories. Recurrences and persistent biochemical or structural disease were not associated with BRAF status. Conclusions Our data are consistent with those of other studies reporting a positive relation between BRAF V600E mutation and poor prognostic factors in PTC, however, the BRAF status did not significantly correlate with a response to therapy. This article is protected by copyright. All rights reserved.

Mutations in the cell cycle checkpoint kinase 2 (CHEK2) tumor suppressor gene are associated with multi-organ cancer susceptibility including cancers of the breast and prostate. A genetic association between thyroid and breast cancer has been suggested, however little is known about the determinants of this association. To characterize the association of CHEK2 mutations with thyroid cancer, we genotyped 468 unselected patients with papillary thyroid cancer and 468 (matched) cancer-free controls for four founder mutations of CHEK2 (1100delC, IVS2 + 1G>A, del5395 and I157T). We compared the family histories reported by patients with a CHEK2 mutation to those of non-carriers. A CHEK2 mutation was seen in 73 of 468 (15.6%) unselected patients with papillary thyroid cancer, compared to 28 of 460 (6.0%) age- and sex-matched controls (OR 3.3; p A, 1100delC or del5395) was associated with a higher risk of thyroid cancer (OR = 5.7; p = 0.006), than was the missense mutation I157T (OR = 2.8; p = 0.0001). CHEK2 mutation carriers reported a family history of breast cancer 2.2 times more commonly than non-carriers (16.4% vs.8.1%; p = 0.05). A CHEK2 mutation was found in seven of 11 women (63%) with multiple primary cancers of the breast and thyroid (OR = 10; p = 0.0004). These results suggest that CHEK2 mutations predispose to thyroid cancer, familial aggregations of breast and thyroid cancer and to double primary cancers of the breast and thyroid.

SummaryContext An activating mutation in the gene BRAF has been correlated with poorer prognosis and more aggressive clinical course in papillary thyroid carcinoma (PTC). We therefore hypothesized that the good prognosis, high 5-year disease-free rate and high survival rate of patients with less aggressive papillary thyroid microcarcinoma (pT1aNo-x) would be associated with a lower incidence of the BRAFV600E mutation. Objectives To evaluate the frequency of the activating mutation BRAFV600E in low-risk papillary thyroid microcarcinoma (pT1aNo-x at the moment of diagnosis) and the association of the mutation with the clinical outcome in a retrospective analysis. Study Design BRAFV600E was characterized in 113 PTC patients diagnosed with pT1aNo-x (one PTC focus with a diameter