Analysis of the association of BRAFV600E mutation and Ki-67 overexpression with clinical and pathological characteristics in papillary thyroid cancer

Еспенбетова, М Ж; Krykpayeva, A; Zamanbekova, Zhanar; Zhumanbaeva, Zhanar; Azizov, Baurzhan Slymovich; Mukanova, Aray; Glushkova, Natalya

doi:10.1007/s00411-021-00904-y

Cited by 4 publications

(4 citation statements)

References 28 publications

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“…We should pay more attention to the expression level of Ki-67 in clinical practice since it may play a role in helping to make better individualized clinical decisions, regardless of other clinicopathological features. By contrast, both studies made by Espenbetova et al 17 and Müssig et al 33 showed PTC patients with high Ki-67 labeling index had a more advanced stage. However, our results did not support this view.…”

Section: Discussionmentioning

confidence: 81%

“…15,16 Regarding thyroid cancer with relatively low expression levels of the Ki-67 labeling index, several previous studies have explored the association between expression levels of the Ki-67 labeling index and the clinical features and prognosis of thyroid cancers, especially in terms of PTC. [17][18][19][20][21] However, whether these associations also existed in Chinses population was not well documented.…”

Section: Introductionmentioning

confidence: 99%

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The Value of Ki-67 Labeling Index in Central Lymph Node Metastasis and Survival of Papillary Thyroid Carcinoma: Evidence From the Clinical and Molecular Analyses

et al. 2023

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Background Recent evidence suggests that the Ki-67 labeling index is associated with lymph node metastasis and the prognosis of papillary thyroid carcinoma (PTC). Methods We retrospectively evaluated the clinicopathological features of consecutive PTC patients between Jan 2019 and Oct 2020 in our medical center. The molecular analysis was also conducted by using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) program. The Chi-square test was performed for the comparison of variables between patients with central lymph node metastasis (CLNM) and not. Besides, univariate and stepwise multivariate logistic regression analyses were further used to determine the risk factors for CLNM in PTC. Results Our results showed that male gender (odd ratio (OR) = 3.02; 95% CI: 1.81-5.04), tumor size >1 cm (OR = 2.81; 95% CI: 1.84-4.29), multifocality (OR = 2.08; 95% CI: 1.31-3.30, and Ki-67 labeling index (>3% and ≤5%: OR = 1.20; 95% CI: .73-1.97; >5%: OR = 3.85; 95% CI: 1.62-9.14) were independent risk factors for CLNM. After excluding the patients with harvested central lymph nodes <3, increased Ki-67 labeling index was still associated with the number of CLNM and the lymph node ratio. Additionally, the expression level of Ki-67 was significantly correlated with a higher N stage and worse disease-free survival in TCGA and validated GSE60542 datasets. Conclusions Higher Ki-67 labeling index (>5%) is significantly associated with the CLNM in PTC patients, like other indicators of the male gender, larger tumor size, and multifocality. Besides, the Ki-67 was also determined to be associated with CLNM and DFS in PTC patients, which may act as an important molecular marker in PTC.

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Section: Discussionmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 99%

The Value of Ki-67 Labeling Index in Central Lymph Node Metastasis and Survival of Papillary Thyroid Carcinoma: Evidence From the Clinical and Molecular Analyses

et al. 2023

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“…Most of the population are descendants of individuals affected by the effects of the tests. A number of epidemiological studies on the health of the population and the risks of developing various neoplasms have been carried out in the region [28,29]. Data on contamination of the territory with trace elements also create prerequisites for aggravating the negative impact on the health of residents living in the region [30].…”

Section: Study Advantages and Limitationsmentioning

confidence: 99%

Preliminary Analysis Of Early And Late Radiation Responses In 3D Image-Guided Brachytherapy For Cervical Cancer

et al. 2022

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Rationale – The use of 3D image-guided brachytherapy (3D-IGBT) allows adequately optimizing the dose distribution to bring a target therapeutic dose to clinical target volume (CTV), thereby minimizing an impact on critical organs, while ensuring a decrease in the incidence and severity of radiation-caused complications. Use of 3D-IGBT also allows improving the quality of life in patients with cervical cancer. Objective – To conduct a preliminary analysis of the incidence of early and late radiation responses in 3D-IGBT of locally advanced cervical cancer (LACC). Materials and Methods – The objects of our study were female patients with stages IIB and IIIB of cervical squamous cell carcinoma, without confirmed metastases, preceding chemotherapy (CHT) and/or radiation therapy (RT), and surgical interventions in this localization, who underwent combined chemoradiotherapy during the study. Results – Statistically significant results were obtained when analyzing the incidence of late radiation responses. It is important to point out that when assessing early toxicity in the main group with 3D-IGBT, grade 3 responses were not diagnosed, while in the control group, they were observed in 4 (9.1%) women. For instance, the manifestation of grade 3 delayed radiation injuries in the rectum was diagnosed in 3 (6.8%) women in the control group, while in the main group, they were not detected. Grade 2 cystitis was observed in a smaller number of women in the group with 3D-IGBT, compared with the control group (9.1% vs. 13.6%, p<0.05). Grade 3 delayed radiation responses in the bladder were diagnosed in 4 (9.1%) women in the control group, whereas among the patients of the main group with 3D-IGBT, they were not recorded at all (p <0.05). Grade II reactions in the vaginal mucosa and cervix were diagnosed more often in the control group (16.7% vs. 13.6%, p<0.05). Conclusion – Hence, the method we have used to optimize the treatment of LACC by means of 3D planning in accordance with toxicity criteria exhibited a definite advantage, compared with RT with 2D planning. Based on the results of our research, we concluded that optimization of RT for LACC using 3D-IGBT created clinically favorable conditions for effective therapy: it reduced the risk of displacement of the applicators and decreased an impact on the patient via reducing the total radiation doses and incidence of severe early and late toxic effects, providing good outcomes of local control regardless of tumor size and clinical stage.

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“…The tall cell variant is the most aggressive tumor, indicating that BRAF mutations are associated with poorer outcomes [9,23]. Other factors associated with the mutation and aggressive tumor phenotype include older age, extrathyroidal tumor invasion, lymph node, and distant metastasis, higher tumor stage, and poorly differentiated cancer [21,22,[24][25][26].…”

Section: Braf Expression In Thyroid Carcinomasmentioning

confidence: 99%

Correlation of the Expression of BRAF V600E Mutation With Various Phenotypic Expressions of Thyroid Neoplasms

Harikrishnan¹,

Kumari²,

Ramkumar³

et al. 2021

Cureus

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We aimed to assess the incidence of the BRAF V600E mutation in thyroid neoplasms at a tertiary care center and its association with various phenotypic features. Methods and materialWe included all cases diagnosed as thyroid neoplasm in the past decade at the Department of Pathology of our institute and obtained their clinical details from the medical records department of the institute after obtaining permission from the authorities and due International Human Epigenome Consortium clearance. We included data on age, sex, clinical presentation, hormone status, and T and N status of the malignant neoplasms. Hematoxylin and eosin (H&E) slides of all cases were evaluated for the type of neoplasm, nuclear features, invasion into the capsule and vascular spaces, extrathyroidal extension, lymph node metastases, mitoses, necrosis, and presence/absence of amyloid. Paraffin blocks of sections with high tumor density and less normal tissue were chosen for evaluation after H&E staining. The slides showing tumors with large areas of hemorrhage, cystic change, or necrosis were excluded. Two primers were used to amplify a 339-bp fragment containing the V600E mutation in exon 15 of BRAF. Tissues were prepared from formalinfixed paraffin-embedded (FFPE) blocks, and DNA was isolated using a standard protocol BRAF NF and BRAF NR Primer Standardized Protocol For FFPE Tissue DNA. Percentages and tables have been used for data presentation. ResultsAmong 47 identified cases, 14 were positive for the BRAF V600E mutation and had papillary carcinoma (n = 9) or follicular neoplasms (n = 5; follicular adenoma, n = 3; follicular carcinoma, n = 2). In the BRAF-positive papillary carcinomas, five cases were aged 20-30 years, eight were female, eight (88.88%) were euthyroid, and one was hypothyroid. Furthermore, 55.55% (5/9 cases) of BRAF-positive cases were stage I, 33.3% (3/9 cases) were stage II, and 0.02% (1/9 cases) were stage III. ConclusionsIn our cohort, 31% of cases of papillary thyroid carcinoma (PTC) and 18.72% of follicular neoplasms expressed the BRAF V600E mutation. BRAF V600E mutation-positive papillary thyroid carcinomas consistently showed all characteristic nuclear features, such as nuclear crowding, overlapping, and grooves.Considering the greater prevalence in the younger age group, the importance of mutation surveillance in PTCs for a total thyroidectomy may be warranted in mutation-positive patients.

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Analysis of the association of BRAFV600E mutation and Ki-67 overexpression with clinical and pathological characteristics in papillary thyroid cancer

Cited by 4 publications

References 28 publications

The Value of Ki-67 Labeling Index in Central Lymph Node Metastasis and Survival of Papillary Thyroid Carcinoma: Evidence From the Clinical and Molecular Analyses

The Value of Ki-67 Labeling Index in Central Lymph Node Metastasis and Survival of Papillary Thyroid Carcinoma: Evidence From the Clinical and Molecular Analyses

Preliminary Analysis Of Early And Late Radiation Responses In 3D Image-Guided Brachytherapy For Cervical Cancer

Correlation of the Expression of BRAF V600E Mutation With Various Phenotypic Expressions of Thyroid Neoplasms

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