Incidence of the CHEK2 Germline Mutation and Its Impact on Clinicopathological Features, Treatment Responses, and Disease Course in Patients with Papillary Thyroid Carcinoma

SIMPLE SUMMARY: The aim of our study was to evaluate whether the CHEK2 mutation was a predictor of poorer clinical course in patients with papillary thyroid cancer. The study included 1547 patients from a single center in Poland, in whom the presence and variant of the CHEK2 mutation were determined. Two hundred and forty patients were found to carry this mutation. We found significant association of the CHEK2 truncating variant with vascular invasion and intermediate or high initial risk of recurrence/persistence, whereas this relationship was not found in case of the missense CHEK2 variant. Neither the truncating nor the missense mutations were associated with worse primary treatment response and outcome of the disease. ABSTRACT: The CHEK2 gene is involved in the repair of damaged DNA. CHEK2 germline mutations impair this repair mechanism, causing genomic instability and increasing the risk of various cancers, including papillary thyroid carcinoma (PTC). Here, we asked whether CHEK2 germline mutations predict a worse clinical course for PTC. The study included 1547 unselected PTC patients (1358 women and 189 men) treated at a single center. The relationship between mutation status and clinicopathological characteristics, treatment responses, and disease outcome was assessed. CHEK2 mutations were found in 240 (15.5%) of patients. A CHEK2 I157T missense mutation was found in 12.3%, and CHEK2 truncating mutations (IVS2 + 1G > A, del5395, 1100delC) were found in 2.8%. The truncating mutations were more common in women (p = 0.038), and were associated with vascular invasion (OR, 6.91; p < 0.0001) and intermediate or high initial risk (OR, 1.92; p = 0.0481) in multivariate analysis. No significant differences in these parameters were observed in patients with the I157T missense mutation. In conclusion, the CHEK2 truncating mutations were associated with vascular invasion and with intermediate and high initial risk of recurrence/persistence. Neither the truncating nor the missense mutations were associated with worse primary treatment response and outcome of the disease.