Relationship between the Expression of CHK2 and p53 in Tumor Tissue and the Course of Papillary Thyroid Cancer in Patients with CHEK2 Germline Mutations.

The aim of this study was to determine whether the expression of CHK2 and p53 in tumor tissue in carriers of germline CHEK2 mutations can serve as a prognostic marker for PTC, and whether CHEK2 and TP53 copy numbers correlates with the course of PTC disease. This study included 156 PTC patients previously tested for the presence of CHEK2. Clinicopathological features, treatment response, disease outcome, and germline mutation status of the CHEK2 gene were assessed with respect to CHK2 and p53 expression, and CHEK2 and TP53 gene copy statuses. In patients with and without a germline mutation in CHEK2 and with higher CHK2 expression, the chances of an excellent treatment response and no evidence of disease were lower than in patients without or with lower CHK2 expression. TP53 deletion was associated with angioinvasion. In patients with a truncating mutation, the chance of a CHEK2 deletion was higher than in patients with WT CHEK2 alone or those with WT CHEK2 and with the missense I157T mutation. Higher CHK2 expression was associated with poorer treatment responses and disease outcomes. Higher CHK2 expression and positive p53 together with a TP53 deletion could be a prognostic marker of unfavorable disease outcomes in patients with germline truncating mutations in CHEK2.

Did Introducing a New Category of Thyroid Tumors (Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features) Decrease the Risk of Malignancy for the Diagnostic Categories in the Bethesda System for Reporting Thyroid Cytopathology?

In 2016, Nikiforov et al. (JAMA Oncol 2:1023-1029, 2016) proposed replacing the term "non-invasive encapsulated follicular variant of papillary thyroid carcinoma" (FVPTC) with the term "non-invasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP). In 2018, to avoid the misdiagnosis of papillary thyroid cancer as NIFTP, the authors proposed changes to the criteria for NIFTP classification. Some previous studies evaluated the impact of NIFTP on the risk of malignancy (ROM) in the fine-needle aspiration cytology (FNAC) diagnostic categories according to the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). However, little is known about the influence of an NIFTP diagnosis on ROM on the basis of the revised criteria. The aim of this study was to assess the influence of NIFTP on ROM using the revised diagnostic criteria. The present study included 998 thyroid nodules that were diagnosed and resected at the same medical center. All specimens with a diagnosis of cancer were reviewed to identify NIFTP according to the revised 2018 criteria. Additionally, molecular diagnostics were performed to detect the BRAF p.V600E mutation and TERT promoter mutations in all the NIFTP cases. The number of cases that met the revised criteria was determined, and the ROM was calculated in each of the FNAC diagnostic categories. Only five cases (2.3% of all papillary thyroid carcinoma diagnoses) were considered NIFTP, according to the 2018 criteria. With respect to the FNAC category, one case was a follicular neoplasm or suspicious for a follicular neoplasm (FN/SFN), three cases were suspicious for malignancy (SM), and one case was malignant (M). The ROM decreased in each of the Bethesda categories (0.7% in FN/SFN, 4.3% in SM, and 0.5% in M) when a diagnosis of NIFTP was taken into account. These reductions were not statistically significant. These data indicate that the NIFTP entity has very little impact on ROM for the diagnostic categories of the Bethesda system.

The influence of the reclassification of NIFTP as an uncertain tumour on risk of malignancy for the diagnostic categories according to the Bethesda system for reporting thyroid cytopathology.

INTRODUCTION: The noninvasive encapsulated, follicular variant of papillary thyroid carcinoma was reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). The exclusion of NIFTP from the group of malignant tumours decreases the risk of malignancy (RoM) as defined by the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). The aim of the present study was to evaluate the RoM for each category in TBSRTC with and without exclusion of NIFTP from the tally of malignancies. MATERIAL AND METHODS: The present study included 998 thyroid nodules cases. All patients underwent diagnostic tests, including fine-needle aspiration cytology, and received surgical treatment. Slides for all resection specimens with a diagnosis of cancer were reviewed to identify NIFTP. The RoM for each of the categories in TBSRTC with and without exclusion of NIFTP from the malignant tumours was evaluated. RESULTS: The RoM decreased with the exclusion of NIFTP from malignant categorisation with the following values for the different TBSRTC categories: non-diagnostic (ND): 0%; benign: 0%; atypia/follicular lesion of undetermined significance (AUS/FLUS): 1.6%; follicular neoplasm/suspicious for follicular neoplasm (FN/SFN): 0.7%; suspicious for malignancy (SUS): 6.9%; and malignant: 2.5%. The difference of 2.5% in the malignant category was statistically significant (p = 0.0253). CONCLUSIONS: The RoM for specific TBSRTC categories needs to be defined for each treatment centre because it is important for the selection of the appropriate surgical treatment for thyroid tumours.

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.