Katarzyna Lizis-Kolus

CHEK2 mutations and the risk of papillary thyroid cancer.

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 < 0.0001). A truncating mutation (IVS2 + 1G>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.

The Delayed Risk Stratification System in the Risk of Differentiated Thyroid Cancer Recurrence

Context There has been a marked increase in the detection of differentiated thyroid carcinoma (DTC) over the past few years, which has improved the prognosis. However, it is necessary to adjust treatment and monitoring strategies relative to the risk of an unfavourable disease course. Materials and Methods This retrospective study examined data from 916 patients with DTC who received treatment at a single centre between 2000 and 2013. The utility of the American Thyroid Association (ATA) and the European Thyroid Association (ETA) recommended systems for early assessment of the risk of recurrent/persistent disease was compared with that of the recently recommended delayed risk stratification (DRS) system. Results The PPV and NPV for the ATA (24.59% and 95.42%, respectively) and ETA (24.28% and 95.68%, respectively) were significantly lower than those for the DRS (56.76% and 98.5%, respectively) (p<0.0001). The proportion of variance for predicting the final outcome was 15.8% for ATA, 16.1% for ETA and 56.7% for the DRS. Recurrent disease was rare (1% of patients), and was nearly always identified in patients at intermediate/high risk according to the initial stratification (9/10 cases). Conclusions The DRS showed a better correlation with the risk of persistent disease than the early stratification systems and allows personalisation of follow-up. If clinicians plan to alter the intensity of surveillance, patients at intermediate/high risk according to the early stratification systems should remain within the specialized centers; however, low risk patients can be referred to endocrinologists or other appropriate practitioners for long-term follow-up, as these patients remained at low risk after risk re-stratification.

Response to therapy of papillary thyroid cancer of known BRAF status

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.

The usefulness of determining the presence of BRAF V600E mutation in fine-needle aspiration cytology in indeterminate cytological results

INTRODUCTION Fine-needle aspiration biopsy (FNAB) is regarded as the gold standard method for the diagnosis of thyroid nodules, but it has its limitations. Additional methods that would improve sensitivity and specificity in the diagnosis of thyroid cancer (TC), especially in indeterminate lesions. Molecular tests seem to be such a tool. BRAF V600E mutation (the most common in TC) can be detected in FNAB and can be potentially a very useful ancillary marker for FNAB practice. The aim of our study was to evaluate the usefulness of the detection of the BRAF V600E mutation in FNAC in the early diagnosis of TC in patients with indeterminate cytology. MATERIAL AND METHOD 2290 FNAB were performed and 147 indeterminate results (group 3, 4, and 5 of the Bethesda system) were obtained. Material from these groups was submitted for molecular tests for the occurrence of BRAF V600E mutation. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the tests were calculated. RESULTS Determining the presence of BRAF V600E mutation in FNAC material in groups 3 and 4 together and in group 5 is associated with sensitivity of TC diagnosis of 37.5% and 81.8%, respectively. In all cases the detection of BRAF V600E mutation was associated with histopathologically proving the presence of TC (specificity of the test - 100%). CONCLUSIONS The presence of BRAF V600E mutation in FNAC material is always associated with the presence of TC. The usefulness of determining the presence of BRAF V600E in FNAC in cytological groups 3 and 4 is associated with low sensitivity in the diagnosis of thyroid cancer. Due to its high specificity BRAF V600E study may be useful in determining the scope of surgery in patients in cytological group 5.

The impact of BMI on clinical progress, response to treatment, and disease course in patients with differentiated thyroid cancer

Introduction Obesity is a serious health problem worldwide, particularly in developed countries. It is a risk factor for many diseases, including thyroid cancer. The relationship between obesity and prognostic factors of thyroid cancer is unclear. Aims We sought to ascertain the relationship between body mass index (BMI) and clinicopathological features increasing the risk of poor clinical course, treatment response, and clinical outcome in patients with differentiated thyroid cancer (DTC). Subjects & methods The study included 1181 patients with DTC (88% women and 12% men) treated at a single center from 2000 to 2016. BMI before surgery and aggressive clinicopathological features, according to the American Thyroid Initial Risk stratification system, were analyzed. The relationship between BMI and initial risk, treatment response, and final status of the disease was evaluated, incorporating the revised 2015 American Thyroid Association guidelines and the 8th edition of the American Joint Committee on Cancer/Tumor-Node-Metastasis (AJCC/TNM) staging system. Patients were stratified according to the World Health Organization classification of BMI. Statistical analysis was performed using univariate and multivariate logistic regression analysis. Results Median follow-up was 7.7 years (1–16 years). There were no significant associations between BMI and extrathyroidal extension (microscopic and gross), cervical lymph node metastasis, or distant metastasis in univariate and multivariate analyses. BMI did not affect initial risk, treatment response or disease outcome. Obesity was more prevalent in men (p = 0.035) and in patients ≥55 years old (p = 0.001). There was no statistically significant relationship between BMI and more advanced TNM stage in patients ≤55 years old (stage I vs. stage II) (p = 0.266) or in patients >55 years old (stage I–II vs. III–IV) (p = 0.877). Conclusions Obesity is not associated with more aggressive clinicopathological features of thyroid cancer. Obesity is not a risk factor for progression to more advanced stages of disease, nor is it a prognostic factor for poorer treatment response and clinical outcome.