scholarly journals THE BRAF MUTATION V600E IN PAPILLARY THYROID CANCER, CLINICAL-MORPHOLOGICALPARALLELES AND PROGNOSIS

2017 ◽  
Vol 22 (1) ◽  
pp. 15-20
Author(s):  
A. A Ivanov ◽  
A. M Avdalyan ◽  
V. J Gerval’d ◽  
E. L Lushnikova ◽  
Yu. N Zorkina ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Lymph Nodes ◽  
Papillary Thyroid Cancer ◽  
Braf Mutation ◽  
Negative Impact ◽  
Morphological Characteristics ◽  
Braf V600e ◽  
Papillary Thyroid ◽  
Ki 67 ◽  
Regional Lymph Nodes

On the material of the 67 cases of papillary thyroid cancer (PTC) authors executed the study of the interrelationship between the BRAF mutation V600E and the forecast, biomolecular and morphological characteristics of the disease. There was implemented the analysis of samples for the presence of 7 KRAS gene mutations, 4 mutations of the PIK3CA gene, mutation BRAF V600E with the revealing of the interrelationship between such biomolecular markers for proliferation and apoptosis as Ki-67, p53, Bcl2. Also there was performed chromogenic hybridization (CISH method) in situ to study the status of the HER2 gene. There was determined the interrelationship between BRAF mutation V600E and clinical indices of prognosis: tumor sizes, capsule invasion, presence of metastases in regional lymph nodes. In addition, there was evaluated the interrelationship between BRAF mutation V600E and 10-years survival rate. No mutation were identified in KRAS, PI3K genes. BRAF mutation V600E was identified in 50 cases (75%). The frequency of V600E in women accounted of 75 ± 6.4%, in men - 67 ± 27.1%. In patients with the presence of V600E the size of a node was slightly less than in the absence of mutations and in 76% of cases did not reach the average value of 1.8 cm. Invasion into the capsule was identified in 35 ± 12.7% cases with a positive BRAF mutation V600E status and in 56 ± 8.4% - in cases with a negative status. Metastases in regional lymph nodes occurred in 36 ± 11.6% in patients with V600E and in 47 ± 18.9% of cases without this mutation. There was obtained the interrelationship between V600E and Ki-67: the average level of the proliferative activity in the presence of the given mutation was 4.4 ± 0.6%, in the absence - 9.4 ± 3.9%. No interrelationship was obtained between V600E and other biomolecular parameters or this interrelationship was tendentious in character. In terms of 10-years survival the groups with or without V600E statistically did not differ. Based on the data, it was possible to say about the absence of the negative impact of V600E on the prognosis in PTC patients

QUANTITATIVE AND QUALITATIVE CHARACTERISTICS OF METASTASES IN REGIONAL LYMPH NODES - RISK FACTORS FOR THE RECURRENCE OF PAPILLARY THYROID CANCER IN CHILDREN AND ADOLESCENTS

2018 ◽  
Vol 64 (2) ◽  
pp. 159-165
Author(s):  
Mikhail Fridman ◽  
Svetlana Mankovskaya ◽  
Olga Krasko
Keyword(s):  
Risk Factors ◽  
Thyroid Cancer ◽  
Lymph Nodes ◽  
Children And Adolescents ◽  
Papillary Thyroid Cancer ◽  
Papillary Thyroid ◽  
Regional Lymph Nodes ◽  
Cancer In Children ◽  
Qualitative Characteristics

Among the factors determining the relapse/persistence of papillary thyroid cancer in children and adolescents the most important are the age of the patient (p= 0.003), the presence of concomitant background pathology (p

scholarly journals High Prevalence and Possible de Novo Formation of BRAF Mutation in Metastasized Papillary Thyroid Cancer in Lymph Nodes

2005 ◽  
Vol 90 (9) ◽  
pp. 5265-5269 ◽  
Author(s):  
Vasily Vasko ◽  
Shuiying Hu ◽  
Guojun Wu ◽  
Jeffrey C. Xing ◽  
Alexandr Larin ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Lymph Nodes ◽  
Papillary Thyroid Cancer ◽  
Braf Mutation ◽  
De Novo ◽  
Papillary Thyroid ◽  
High Prevalence

scholarly journals Association Between BRAF V600E Mutation and Recurrence of Papillary Thyroid Cancer

2015 ◽  
Vol 33 (1) ◽  
pp. 42-50 ◽  
Author(s):  
Mingzhao Xing ◽  
Ali S. Alzahrani ◽  
Kathryn A. Carson ◽  
Young Kee Shong ◽  
Tae Yong Kim ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Multicenter Study ◽  
Braf Mutation ◽  
Prognostic Value ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Disease Stage ◽  
Papillary Thyroid ◽  
Recurrence Rates

Purpose To investigate the prognostic value of BRAF V600E mutation for the recurrence of papillary thyroid cancer (PTC). Patients and Methods This was a retrospective multicenter study of the relationship between BRAF V600E mutation and recurrence of PTC in 2,099 patients (1,615 women and 484 men), with a median age of 45 years (interquartile range [IQR], 34 to 58 years) and a median follow-up time of 36 months (IQR, 14 to 75 months). Results The overall BRAF V600E mutation prevalence was 48.5% (1,017 of 2,099). PTC recurrence occurred in 20.9% (213 of 1,017) of BRAF V600E mutation–positive and 11.6% (125 of 1,082) of BRAF V600E mutation–negative patients. Recurrence rates were 47.71 (95% CI, 41.72 to 54.57) versus 26.03 (95% CI, 21.85 to 31.02) per 1,000 person-years in BRAF mutation–positive versus –negative patients (P < .001), with a hazard ratio (HR) of 1.82 (95% CI, 1.46 to 2.28), which remained significant in a multivariable model adjusting for patient sex and age at diagnosis, medical center, and various conventional pathologic factors. Significant association between BRAF mutation and PTC recurrence was also found in patients with conventionally low-risk disease stage I or II and micro-PTC and within various subtypes of PTC. For example, in BRAF mutation–positive versus –negative follicular-variant PTC, recurrence occurred in 21.3% (19 of 89) and 7.0% (24 of 342) of patients, respectively, with recurrence rates of 53.84 (95% CI, 34.34 to 84.40) versus 19.47 (95% CI, 13.05 to 29.04) per 1,000 person-years (P < .001) and an HR of 3.20 (95% CI, 1.46 to 7.02) after adjustment for clinicopathologic factors. BRAF mutation was associated with poorer recurrence-free probability in Kaplan-Meier survival analyses in various clinicopathologic categories. Conclusion This large multicenter study demonstrates an independent prognostic value of BRAF V600E mutation for PTC recurrence in various clinicopathologic categories.

scholarly journals Preoperative Factors Associated with Extrathyroidal Extension in Papillary Thyroid Cancer

2020 ◽  
Vol 9 (5) ◽  
pp. 256-262 ◽  
Author(s):  
Chi-Yu Kuo ◽  
Po-Sheng Yang ◽  
Ming-Nan Chien ◽  
Shih-Ping Cheng
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Tumor Size ◽  
Braf Mutation ◽  
Extrathyroidal Extension ◽  
Additive Models ◽  
Braf V600e ◽  
Papillary Thyroid ◽  
Factors Associated ◽  
Preoperative Factors

Objective: Extrathyroidal extension may not be accurately recognized during thyroidectomy and can increase the risk of positive margins and even recurrence. This study aimed to investigate the preoperative factors associated with extrathyroidal extension. Methods: We analyzed 887 patients with papillary thyroid cancer (PTC) who underwent surgery in the period of 2005–2017. Binary logistic regression analyses and generalized additive models were used to identify associations. Results: Minimal extrathyroidal extension was present in 233 (26%) patients and advanced extrathyroidal extension was found in 60 (7%) patients. Age, BMI, and tumor size were independent predictors of all or advanced extrathyroidal extension. Among the 493 patients whose BRAF mutation status was available, age (OR = 1.025), BMI (OR = 1.091), tumor size (OR = 1.544), and BRAF V600E mutation (OR = 2.311) were independently associated with extrathyroidal extension. Conclusions: Older age, a greater BMI, a larger tumor size, and presence of the BRAF mutation were predictive of extrathyroidal extension. These factors should be taken into consideration in decision-making before surgery is performed.

Recurrence in regional lymph nodes after total thyroidectomy and neck dissection in patients with papillary thyroid cancer

Oral Oncology ◽  
2015 ◽  
Vol 51 (2) ◽  
pp. 164-169 ◽  
Author(s):  
Ji-young Joo ◽  
Jun Jin ◽  
Sung Tae Seo ◽  
Young Chang Lim ◽  
Ki-Sang Rha ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Lymph Nodes ◽  
Total Thyroidectomy ◽  
Neck Dissection ◽  
Papillary Thyroid Cancer ◽  
Papillary Thyroid ◽  
Regional Lymph Nodes

scholarly journals BRAF V600E Maintains Proliferation, Transformation, and Tumorigenicity of BRAF-Mutant Papillary Thyroid Cancer Cells

2007 ◽  
Vol 92 (6) ◽  
pp. 2264-2271 ◽  
Author(s):  
Dingxie Liu ◽  
Zhi Liu ◽  
Stephen Condouris ◽  
Mingzhao Xing
Keyword(s):  
Cell Proliferation ◽  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Nude Mice ◽  
Braf Mutation ◽  
Soft Agar ◽  
Braf V600e ◽  
Papillary Thyroid ◽  
Small Interference Rna

Abstract Context: Although the BRAF V600E mutant can initiate the formation of papillary thyroid cancer (PTC), it is unclear whether it is required to maintain cell proliferation, transformation, and tumor growth of BRAF mutation-harboring PTC. Objective: The aim of the study was to investigate whether BRAF V600E is required for the proliferation, transformation, and tumorigenicity of BRAF mutation-harboring PTC cells. Design: We addressed this issue using BRAF small interference RNA (siRNA) to transfect stably several BRAF mutation-harboring PTC cell lines, isolated clones with stable suppression of BRAF, and assessed their ability to proliferate, transform, and grow xenograft tumors in nude mice. Results: PTC cell proliferation and transformation were suppressed in specific BRAF siRNA clones, but not in control scrambled siRNA clones. Specifically, taking the advantage of stable BRAF knockdown, we were able to show continued suppression of PTC cell proliferation and transformation, or anchorage-independent colony formation in soft agar, after long-term culture. Moreover, we also demonstrated that in vivo tumorigenicity and growth of tumors from the specific BRAF siRNA cell clones in nude mice were suppressed compared with control clones. Conclusions: BRAF V600E is not only an initiator of PTC as demonstrated previously but is also a maintainer of proliferation, transformation, and tumorigenicity of PTC cells harboring BRAF mutation, and growth of tumors derived from such cells continues to depend on BRAF V600E. These results provide further support for potentially effective therapy targeted at BRAF for BRAF mutation-harboring PTC.

scholarly journals BRAF V600E Mutation-Assisted Risk Stratification of Solitary Intrathyroidal Papillary Thyroid Cancer for Precision Treatment

2017 ◽  
Vol 110 (4) ◽  
pp. 362-370 ◽  
Author(s):  
Yueye Huang ◽  
Shen Qu ◽  
Guangwu Zhu ◽  
Fei Wang ◽  
Rengyun Liu ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Risk Stratification ◽  
Papillary Thyroid Cancer ◽  
Braf Mutation ◽  
Hazard Ratio ◽  
Braf V600e ◽  
Independent Effect ◽  
Papillary Thyroid ◽  
Wild Type ◽  
Recurrence Rates

Abstract Background Precise risk stratification-based treatment of solitary intrathyroidal papillary thyroid cancer (SI-PTC) that is larger than 1.0 cm and 4.0 cm or less is undefined. Methods A genetic-clinical risk study was performed on BRAF V600E in 955 patients (768 women and 187 men) with SI-PTC, with median age of 46 years and median clinical follow–up time of 64 months at 11 medical centers in six countries. The chi-square test or, for analyses with small numbers, Fisher’s exact test was performed to compare recurrence rates. Recurrence-free probability was estimated by Kaplan-Meier (KM) analysis, and the independent effect of BRAF mutation on the recurrence was analyzed by Cox regression and Cox proportional hazard analyses. All statistical tests were two-sided. Results Recurrence of SI-PTC larger than 1.0 cm and 4.0 cm or less was 9.5% (21/221) vs 3.4% (11/319) in BRAF mutation vs wild-type BRAF patients, with a hazard ratio (HR) of 3.03 (95% confidence interval [CI] = 1.46 to 6.30) and a patient age- and sex-adjusted hazard ratio of 3.10 (95% CI = 1.49 to 6.45, P = .002). Recurrence rates of SI-PTC larger than 2.0 cm and 4.0 cm or less were 16.5% (13/79) vs 3.6% (5/139) in mutation vs wild-type patients (HR = 5.44, 95% CI = 1.93 to 15.34; and adjusted HR = 5.58, 95% CI = 1.96 to 15.85, P = .001). Recurrence rates of SI-PTC larger than 3.0 cm and 4 cm or less were 30.0% (6/20) vs 1.9% (1/54) in mutation vs wild-type patients (HR = 18.40, 95% CI = 2.21 to 152.98; and adjusted HR = 14.73, 95% CI = 1.74 to 124.80, P = .01). Recurrences of mutation-positive SI-PTC were comparable with those of counterpart invasive solitary PTC, around 20% to 30%, in tumors larger than 2.0 cm to 3.0 cm. BRAF mutation was associated with a statistically significant decrease in recurrence-free patient survival on KM analysis, particularly in SI-PTC larger than 2.0 cm and 4.0 cm or less. Similar results were obtained in conventional SI-PTC. The negative predictive values of BRAF mutation for recurrence were 97.8% (95% CI = 96.3% to 98.8%) for general SI-PTC and 98.2% (95% CI = 96.3% to 99.3%) for conventional SI-PTC. Conclusions BRAF V600E identifies a subgroup of SI-PTC larger than 1.0 cm and 4.0 cm or less, particularly tumors larger than 2.0 cm and 4.0 cm or less, that has high risk for recurrence comparable with that of invasive solitary PTC, making more aggressive treatment reasonable.

scholarly journals Concomitant BRAF Mutation in Hairy Cell Leukemia and Papillary Thyroid Cancer

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5140-5140
Author(s):  
Shehab Mohamed ◽  
Mohamed A Yassin ◽  
Abdulqadir Jeprel Nashwan ◽  
Halima El Omri ◽  
Firyal Ibrahim ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Hairy Cell Leukemia ◽  
Braf Mutation ◽  
Braf V600e ◽  
Hairy Cell ◽  
Papillary Thyroid ◽  
Cell Leukemia ◽  
Cell Neoplasm

Abstract Hairy cell leukemia (HCL) is an uncommon but distinct form of mature B-cell neoplasm that originates from activated late B-cells. It represents only 2% of all adult lymphoid leukemia; patients are predominantly middle-aged to elderly males with a median age of 50 years and is characterized by pancytopenia, monocytopenia and usually associated with massive splenomegaly. HCL associated with BRAF mutation 100% of cases, it's associated with hematological and oncological malignancies such as melanoma and papillary thyroid cancer with positive BRAF in 40 % of cases. Although the association of both cancers (HCL & papillary thyroid cancer) with BRAF mutation is well established in the literature, up to our knowledge, this specific combination has not been previously reported in one patient. Here we report a case of 48-year old Lebanese male, who presented to with bilateral hip pain and found to have lytic bone lesions on both x-ray and MRI. HIS CBC were normal and abdominal US didn't show any splenomegaly. Work-up for myeloma were negative. Bone marrow examination and flow cytometry results confirmed the diagnosis of hairy cell leukemia. The patient treated with cladrabine. Patient responded but have continues fever, PUO included Piston tomography showed abnormal uptake in thyroid. Ultrasound and final needle aspiration diagnose him as case of papillary thyroid cancer. He was treated with total thyroidectomy and followed up with RAI 30 micori. We sent BRAF from both bone marrow biopsy and thyroid tissue which turn out positive in both. The mutation results in substitution of adenine for thymine at position 1799 in exon 15 of the BRAF that replaces Valine (V) by glutamate (E) at amino acid 600(BRAF V600E). Although the BRAF V600E mutation is frequently present in different neoplasms, such as melanoma, papillary thyroid cancer, non-small cell lung cancer, colorectal cancer and Langerhans cell histiocytosis (X), within the lymphoid neoplasms, the BRAFV600E mutation is found to be highly specific for HCL and testing for this mutation is particularly useful in differentiating classic HCL from other B- cell neoplasm with overlapping features, such as HCL variant Mutation in BRAF (particularly V600E) in HCL remarkably increase the BRAF kinase activity renders the protein constitutively active, phosphorylating then ERK as a monomers independent from upstream regulatory signals or in a RAS-independent manner leading to constitutive activation of RAF-MEK-ERK signaling pathway and enhanced survival of leukemic hairy cells, similar to what occurs in other BRAF-mutated tumors as papillary thyroid carcinomas Other BRAF mutations outside exon 15 were rarely reported as exon 11 F468C and D449E mutations. We emphasize on the link of BRAF mutation in HCL and papillary thyroid cancer. The biology has been established but never in real clinical case. We recommend having high clinical suspicion and sending BRAF mutation in those types of cancers and link it with other possible abnormal findings, as might detect more cases of similar association. Disclosures No relevant conflicts of interest to declare.

scholarly journals INFLUENCE OF BRAF MUTATION ON CLINICAL AND PATHOLOGICAL MANIFESTATIONS OF PAPILLARY THYROID CANCER

2020 ◽  
Vol 23 (2) ◽  
pp. 92-99
Author(s):  
S. A. Lukyanov ◽  
S. V. Sergiyko ◽  
S. E. Titov ◽  
G. O. Shcherbakov
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Braf Mutation ◽  
Clinical Stage ◽  
Molecular Genetic ◽  
Papillary Thyroid ◽  
Regional Lymph Nodes ◽  
Clinical Criteria ◽  
Increased Risk ◽  
Risk Of Relapse

Stratifications of the risk of recurrence and mortality in papillary thyroid cancer (PTC) are currently based on clinical criteria. In order to provide a more accurate assessment of the risk of relapse, new criteria, such as molecular genetic markers, are constantly being sought. The most studied of these markers is the BRAF mutation. The aim of the work was to study the dependence of clinical and pathological manifestations of papillary thyroid cancer on the presence of a BRAF mutation. The retrospective study included 212 patients with PTC. The dependence of the BRAF mutation on the patient’s gender, age, multifocality, presence of regional and remote metastases, extrathyroid invasion, clinical stage, and risk of relapse was studied. A single tumor was found in 196 (92.4%) cases, and a multifocal one in 16 (7.6%). Macroscopic extrathyroid invasion was observed in 80 (37.7%) patients. Metastases in regional lymph nodes were found in 83 (39.2%) patients, in 12 (5.7%) cases, the presence of distant metastases was detected. It was found that the BRAF mutation was present in 128 (60.4%) patients. There was no statistically significant association between the presence of the mutation and clinical and pathological manifestations of PTC, except for age. The incidence of the BRAF mutation in patients with PTC in young, middle, elderly and senile age was 3.8-35 times higher than in children and young men. It was found that the frequency of detection of the BRAF mutation increases with the age of the patient and has a linear relationship. It was concluded that the BRAF mutation can’t be used as an isolated marker of aggressive flow and a criterion indicating an increased risk of relapse of PTC.

scholarly journals MOLECULAR TYPES IN THE PROGNOSIS OF PAPILLARY THYROID CANCER BASED ON THE ANALYSIS OF THE STATUS OF BRAF V600E, INDEX AND KI-67 EXPRESSION

2017 ◽  
Vol 22 (4) ◽  
pp. 188-193
Author(s):  
Anatoly A. Ivanov ◽  
A. M Avdalyan ◽  
V. J Gerval'd ◽  
E. L Lushnikova ◽  
Yu. N Zorkina ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Real Time ◽  
Papillary Thyroid Cancer ◽  
Real Time Pcr ◽  
Braf V600e ◽  
Type Ii ◽  
Papillary Thyroid ◽  
Molecular Type ◽  
Ki 67 ◽  
The Status

The aim of our research was to determine the possibilities to stratify patients with papillary thyroid cancer (PTC) on the group’s forecast, depending on the status of the mutation BRAF v600e and Ki-67 expression. The study included 89 PTC patients with the known prognosis for the period of 2005-2015. They were treated in the Altai regional oncology center and underwent surgery for PTC over the period of 2005-2013. Mutation p. Val600Glu (V600E) BRAF gene was determined with the use of allele-specific real-time PCR kit «Real-time-PCR-BRAF-V600E («BioLink»)». Immunohistochemical examination was performed with antibodies Ki-67 (clone MIB1, «DAKO») on stainer «Ventana XT» according to standard protocols. We revealed BRAF V600E not to be an independent predictor. Different variants of PTC, depending on the level of expression of Ki-67 in combination with a mutation of BRAF V600E was allowed to identify 3 groups of molecular types of PTC: a lack of mutation and a low Ki-67 (type I), with mutation and a low Ki-67 (type II) and with the presence and/or absence of a mutation and high level Ki-67 (type III). I molecular type PTC is the most favorable from the point of view of survival: 100% of patients live 10 years. Molecular type II is characterized by an intermediate prognosis: 76% of patients lived out up to 10 years. Molecular type III is characterized by the poor prognosis: only 36.8 percent of cases lived up to 10 years. In multivariate analysis of survival in PTC patients the independent prognostic factor happened to be the molecular type of tumor. In this case χ2 = 35 at p ≤ 0.000005.

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