The ability of cancer to metastasize is regulated by various signaling pathways, including transforming growth factor β (TGFβ), also implicated in the upregulation of Snail-1 transcription factor in malignant neoplasms. B-type Raf kinase gene (BRAF)V600E, the most common driving mutation in papillary thyroid carcinoma (PTC), induces epithelial to mesenchymal transition (EMT) in thyroid cancer cells through changes in the Snail-1 level, increasing cell migration and invasion. However, little is known about the mechanism of Snail-1 and BRAFV600E relations in humans. Our study included 61 PTC patients with evaluated BRAFV600E mutation status. A total of 18 of those patients had lymph node metastases-of whom 10 were BRAFV600E positive, and 8 negative. Our findings indicate that the expression of Snail-1, but not TGFβ1, correlates with the metastatic phenotype in PTC. This is the first piece of evidence that the upregulation of Snail-1 corresponds with the presence of BRAFV600E mutation and increased expression of Snail-1 in metastatic PTC samples is dependent on BRAFV600E mutation status.
In 2016, encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) was reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP).In 2018 the criteria for NIFTP were widened by the inclusion of the complete lack of papillae.Secondary criteria, which include molecular examination, are helpful but not required for NIFTP diagnose.The aim of this study was to assess the molecular background of NIFTP and to answer the question if the aplication of revised criteria for NIFTP diagnosis is associated with the lack of oncogenic mutation.Repeat histopathological assessment of 1117 cases of papillary thyroid carcinoma (PTC) from 2000-2016 was conducted.Using initial (2016) and revised (2018) diagnostic criteria, NIFTP was diagnosed in 23 and 13 patients respectively.50 tumor genes hotspots mutation analysis was conducted.BRAF V600E mutations were detected in patients who fulfilled only initial NIFTP criteria.Other high-risk mutations (TP53) were found in both groups of patients.The application of restrictive, revised diagnostic criteria for NIFTP negates the need for BRAF V600E examination, but these tumors still can harbor other high-risk oncogenic mutations nonetheless.Thus, molecular examination should be considered as a necessary step in NIFTP diagnostic process.
Metastasis to the thyroid gland is uncommon compared with the frequency of primary thyroid tumors. The most common types of cancer metastatic to the thyroid gland include: carcinoma of kidney, lung, breast ovary and melanoma. In the literature, we find descriptions of cases of metastatic breast cancer patients previously diagnosed with breast carcinoma, resulting from the development of cancer. However, breast cancer metastasis to the thyroid gland, as the first manifestation of the disease is rare. Case report: 73-year-old patient with fast-growing tumor of the right thyroid lobe was admitted to the Department of Endocrinology, Holy Cross Cancer Center to diagnosis and further treatment. Many years ago she was seen because of thyroid nodular disease in euthyroid stage. Before admission fine needle aspiration biopsy of the right lobe of the thyroid nodule was done. The study found the group and individual atypical cells that suggest medullary or insular thyroid cancer. Based on cytological diagnosis-including immunohistochemistry was suspected metastatic breast cancer. On the basis of further studies revealed the presence of breast cancer metastatic to the thyroid gland. Each rapidly growing thyroid tumor should be differentiated from secondary changes in the absence of previous clinical data accompanying cancer. Immunohistochemical examination is very helpful in the clinical diagnosis.
Thyroid cancer (TC) has one of the fastest increasing incidences worldwide and primarily involves papillary thyroid cancer (PTC). The BRAF(V600E) mutation is the most common genetic alteration identified in PTC. There are few data concerning an association between the rising incidence of PTC and the increasing prevalence of BRAF-positive cases. Environmental factors such as iodine intake may be responsible for the changing molecular features of PTC. The aim of this study was to evaluate probable variations in the frequency of the BRAF(V600E) mutation in PTC that were diagnosed at a single institution over 14 years in Poland, a country with a demonstrated improvement in iodine supplementation in the early 21st century.Time-dependent trends in the prevalence of the BRAF(V600E) mutation during three time periods (2000-2004, 2005-2009, and 2010-2013) were analyzed. The BRAF mutation was genotyped using direct sequencing, allele-specific polymerase chain reaction (PCR), and real-time PCR in 723 unselected cases of PTC that were diagnosed in 2000-2013. Trends in the clinicopathologic characteristics of all PTCs and BRAF(V600E)-positive PTCs were also analyzed.The proportion of PTCs with mutations significantly increased over the study period (54.8% vs. 70.6%; p = 0.001). The median tumor size of all and BRAF-positive tumors decreased (p = 0.008 and p = 0.001, respectively) and correlated with an increase in the proportion of all and mutated microcarcinomas (p = 0.003 and p = 0.003, respectively). A decrease in all and mutated tumors between 2 and 4 cm was also observed (p = 0.002 and p = 0.006, respectively). A significant decrease in tumors ≥ 4 cm in size was only observed in BRAF-positive cases (p = 0.017). The proportion of classic PTC with BRAF(V600E) mutation was observed to increase (57.6% vs. 74.4%; p = 0.001) and was stable for the follicular variant of PTC (p = 0.336).The prevalence of the BRAF(V600E)mutation increased significantly in PTCs diagnosed in the authors' institution. Improved detection and several causative factors, most likely environmental and changes in iodine intake, may contribute to the increasing occurrence of TC.
Differentiated papillary thyroid cancer (PTC) is the most common cancer of the endocrine system. PTC has a very good prognosis and a high 5 year survival rate; however, some patients are unresponsive to treatment, and their diagnosis eventually results in death. Recent efforts have focused on searching for prognostic and predictive factors that may enable treatment personalization and monitoring across the course of the disease. The presence of the BRAF mutation is considered to contribute to the risk of poor clinical course, according to American Thyroid Association (ATA) recommendations. The method used for genotyping can impact the predicted mutation frequency; however, ATA recommendations do not address this issue. We evaluated the molecular diagnostic (BRAF p.V600E mutation) results of 410 patients treated for PTC. We thoroughly analyzed the impact of three different BRAF mutation detection methods, Sanger Sequencing (Seq), allele-specific amplification PCR (ASA-PCR), and quantitative PCR (qPCR), on the frequency of mutation detection in 399 patients. Using Seq, we detected the BRAF mutation in 37% of patients; however, we were able to detect BRAF mutations in 57% and 60% of patients using the more sensitive ASA-PCR and qPCR technologies, respectively. Differences between methods were particularly marked in the thyroid papillary microcarcinoma group; BRAF p.V600E mutations were found in 37% of patients using Seq and 63% and 66% of patients using ASA-PCR and qPCR, respectively. We also evaluated how these different diagnostic methods were impacted by DNA quality. Applying methods with different sensitivities to the detection of BRAF p.V600E mutations may result in different results for the same patient; such data can influence stratification of patients into different risk groups, leading to alteration of treatment and follow-up schemes.
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.
Summary Objective 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 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 disease and structural disease. Patients Unselected PTC cases with known BRAF status diagnosed from 2000 to 2013 and actively monitored at one institution (n=723) were reviewed retrospectively. 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, was analysed. 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.
