Genetic Changes in Thyroid Cancers and the Importance of Their Preoperative Detection in Relation to the General Treatment and Determination of the Extent of Surgical Intervention—A Review

Hložek, Jiří; Pekova, Barbora; Rotnágl, Jan; Holý, Richard; Astl, Jaromı́r

doi:10.3390/biomedicines10071515

Cited by 8 publications

(3 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 8 The main known genetic causes of thyroid cancer include point mutations in the BRAF, RAS, TERT, RET , and TP53 genes and the fusion genes RET/PTC, PAX8/PPAR-γ , and NTRK . 9 Fusion gene positive PTCs were associated with more aggressive behavior disease than fusion gene negative PTCs. 10 A comprehensive study reported by Pekova et al recently identified that RET fusion was associated with a 100% probability of malignancy.…”

Section: Introductionmentioning

confidence: 94%

Age and BRAFV600E Mutation Stratified Patients with Cytologically Benign Thyroid Nodules

Huang,

Liu,

Han

et al. 2023

IJGM

View full text Add to dashboard Cite

Our objective was to evaluate the diagnostic performance of BRAF V600E mutation for malignant, and to identify clinical characteristics associated with positive BRAF V600E mutation in low-risk cytological and ultrasound diagnostic thyroid nodules. This aims to identify patients who may benefit from BRAF V600E mutation testing and subsequent surgical intervention. Patients and Methods: We analysis the clinical characteristics correlated with BRAF V600E mutation in our detection cohort, including 204 patients with 217 thyroid nodules, and separate analyses were performed in 103 thyroid nodules with benign cytological result. Signaling pathway and immune response associated with age and BRAF V600E mutation status were also evaluated in Asian patients with thyroid cancer from the Cancer Genome Atlas (TCGA) dataset. Results:The positive BRAF V600E mutation was significantly associated with higher Ultrasound (US) classification (p<0.001) and fineneedle aspiration (FNA) categories (p<0.001). BRAF V600E mutation as a risk factor for malignancy, showing the optimal diagnostic efficacy for malignancy combined with FNA categories, with the AUC was 0.923. Otherwise, BRAF V600E mutation is a risk factor in screening malignancy in low-risk FNA and US classification, which is significant correlation with patients age. Patients over 50 years old exhibiting a higher percentage of positive BRAF V600E mutation when both ultrasound and FNA results indicate benign conditions, with higher risk of malignancy. Conclusion: BRAF V600E mutation is an accurate adjunctive diagnostic marker on FNA to screen malignancy. In low risk of both ultrasound and FNA results, the positive BRAF V600E was significant increased in patients over 50 years old, which have higher risk of malignancy. Thus, the BRAF V600E mutation detection and further surgery should be strengthened in older patients with benign cytological and US results thyroid nodules.

show abstract

Section: Introductionmentioning

confidence: 94%

Age and BRAFV600E Mutation Stratified Patients with Cytologically Benign Thyroid Nodules

Huang,

Liu,

Han

et al. 2023

IJGM

View full text Add to dashboard Cite

show abstract

“…Despite its favorable prognosis, the idea has been advanced that clinicopathological features and the presence of some genetic alterations can influence their progression [9]. Accurate pre-surgical diagnosis is crucial to decide the optimal medical or surgical treatment [10].…”

Section: Introductionmentioning

confidence: 99%

Comparative Cyto-Histological Genetic Profile in a Series of Differentiated Thyroid Carcinomas

Matos,

Pinto,

Alves

et al. 2024

Diagnostics

View full text Add to dashboard Cite

Introduction: Molecular tests can contribute to improve the preoperative diagnosis of thyroid nodules. Tests available are expensive and not adapted to different populations. Aim: This study aimed to compare the cyto-histological genetic profile and to evaluate the reliability of molecular tests using ultrasound-guided fine needle aspiration cytology (US-FNAC) in accurately diagnosing differentiated thyroid carcinomas (DTCs) and predicting biologic behavior of papillary thyroid carcinomas (PTCs). Materials and Methods: The series included 259 patients with paired cyto-histological samples totaling 518 samples. The genetic alterations were analyzed via PCR/Sanger sequencing. The association with clinicopathologic features was evaluated in PTCs. Results/Discussion: From the 259 patients included, histologies were 50 (19.3%) benign controls and 209 (80.7%) DTC cases, from which 182 were PTCs; cytologies were 5.8% non-diagnostic, 18.2% benign, 39% indeterminate, and 37.1% malignant. In histology, indeterminate nodules (n = 101) were 22.8% benign and 77.2% malignant. Mutation frequencies in cytology and histology specimens were, respectively, TERTp: 3.7% vs. 7.9%; BRAF: 19.5% vs. 25.1%; and RAS: 11% vs. 17.5%. The overall cyto-histological agreement of the genetic mutations was 94.9%, with Cohen’s k = 0.67, and in indeterminate nodules agreement was 95.7%, k = 0.64. The identified mutations exhibited a discriminative ability in diagnosing DTC with a specificity of 100% for TERTp and BRAF, and of 94% for RAS, albeit with low sensitivity. TERTp and BRAF mutations were associated with aggressive clinicopathological features and tumor progression in PTCs (p < 0.001). The obtained good cyto-histological agreement suggests that molecular analysis via US-FNAC may anticipate the genetic profile and the behavior of thyroid tumors, confirming malignancy and contributing to referring patients to surgery.

show abstract

“…The prognosis of PTCs is usually favorable, but the association of some clinicopathological characteristics and the presence of some genetic mutations may affect their progression and behavior [ 5 ]. An accurate diagnosis in the pre-surgical phase is essential to optimize medical or surgical treatment and to avoid unnecessary surgeries and complications [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Cyto-Histological Profile of MicroRNAs as Diagnostic Biomarkers in Differentiated Thyroid Carcinomas

Matos,

Pinto,

Alves

et al. 2024

Genes

View full text Add to dashboard Cite

Introduction: The repertoire of microRNAs (miRNAs) in thyroid carcinomas starts to be elucidated. Among differentiated thyroid carcinomas (DTCs), papillary thyroid carcinoma (PTC) is the most frequent. The assessment of miRNAs expression may contribute to refine the pre-surgical diagnosis in order to obtain a personalized and more effective treatment for patients. Aims: This study aims to evaluate (1) the miRNAs in a series of DTCs, and their association with the presence of selected genetic mutations in order to improve diagnosis and predict the biologic behavior of DTC/PTC. (2) The reliability of molecular tests in Ultrasound-guided Fine Needle Aspiration Cytology (US-FNAC) for a more precise preoperative diagnosis. Material and Methods: This series includes 176 samples (98 cytology and 78 histology samples) obtained from 106 patients submitted to surgery, including 13 benign lesions (controls) and 93 DTCs (cases). The microRNA expression was assessed for miR-146b, miR-221, miR-222, and miR-15a through quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The results were analyzed by the 2−ΔΔCT method, using miR16 as an endogenous control. Regarding PTC diagnosis, the discriminative ability of miRNAs expression was assessed by the area under the Receiver Operating Characteristic Curve (AUC). In PTCs, the association of miRNAs expression, clinicopathological features, and genetic mutations (BRAF, RAS, and TERTp) was evaluated. Results/Discussion: All the analyzed miRNAs presented a tendency to be overexpressed in DTCs/PTCs when compared with benign lesions, both in cytology and histology samples. In cytology, miRNAs expression levels were higher in malignant tumors than in benign tumors. In histology, the discriminative abilities regarding PTC diagnosis were as follows: miR-146b (AUC 0.94, 95% CI 0.87–1), miR-221 (AUC 0.79, 95% CI 0.68–0.9), miR-222 (AUC 0.76, 95% CI 0.63–0.89), and miR-15a (AUC 0.85, 95% CI 0.74–0.97). miR-146b showed 89% sensitivity (se) and 87% specificity (sp); miR-221 se = 68.4, sp = 90; miR-222 se = 73, sp = 70; and mi-R15a se = 72, sp = 80. MicroRNAs were associated with worst-prognosis clinicopathological characteristics in PTCs (p < 0.05), particularly for miR-222. Our data reveal a significant association between higher expression levels of miR-146b, miR-221, and miR-222 in the presence of the BRAF mutation (p < 0.001) and miR-146b (p = 0.016) and miR-221 (p = 0.010) with the RAS mutation, suggesting an interplay of these mutations with miRNAs expression. Despite this study having a relatively small sample size, overexpression of miRNAs in cytology may contribute to a more precise preoperative diagnosis. The miRNAs presented a good discriminative ability in PTC diagnosis. The association between the miRNAs expression profile and genetic alterations can be advantageous for an accurate diagnosis of DTCs/PTCs in FNAC.

show abstract

Genetic Changes in Thyroid Cancers and the Importance of Their Preoperative Detection in Relation to the General Treatment and Determination of the Extent of Surgical Intervention—A Review

Cited by 8 publications

References 53 publications

Age and BRAFV600E Mutation Stratified Patients with Cytologically Benign Thyroid Nodules

Age and BRAFV600E Mutation Stratified Patients with Cytologically Benign Thyroid Nodules

Comparative Cyto-Histological Genetic Profile in a Series of Differentiated Thyroid Carcinomas

Cyto-Histological Profile of MicroRNAs as Diagnostic Biomarkers in Differentiated Thyroid Carcinomas

Contact Info

Product

Resources

About