Molecular testing in thyroid cancer diagnosis and management

Sipos, Jennifer A.; Ringel, Matthew D.

doi:10.1016/j.beem.2022.101680

Cited by 13 publications

(15 citation statements)

References 115 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most of the TC primary driver oncogenes activate the mitogen activated protein kinase (MAPK) and the PI3K pathways ( 22 – 24 ); the alterations involving these pathways are the most found in ATC and PDTC ( 20 ). BRAF V600E and RAS-like mutations, including three highly homologous isoforms (NRAS, KRAS and HRAS) are the most common found in TC.…”

Section: Genetic Pathways and Epigenetic Mechanisms Implicated In Tc ...mentioning

confidence: 99%

“…Furthermore, BRAF V600E inhibitors have showed promising results for advanced DTC in phase II studies ( 92 , 93 ). Ultimately, the activity of FDA-approved immune checkpoint inhibitors (such as anti-PD1 and anti-PDL1) is also routinely tested in TC samples and predictors of response are the detection of MSI and high mutational burden ( 24 ).…”

Section: Molecular Driven Therapiesmentioning

confidence: 99%

See 1 more Smart Citation

Molecular features of aggressive thyroid cancer

et al. 2022

View full text Add to dashboard Cite

Poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) have a worse prognosis with respect to well differentiated TC, and the loss of the capability of up-taking 131I is one of the main features characterizing aggressive TC. The knowledge of the genomic landscape of TC can help clinicians to discover the responsible alterations underlying more advance diseases and to address more tailored therapy. In fact, to date, the antiangiogenic multi-targeted kinase inhibitor (aaMKIs) sorafenib, lenvatinib, and cabozantinib, have been approved for the therapy of aggressive radioiodine (RAI)-resistant papillary TC (PTC) or follicular TC (FTC). Several other compounds, including immunotherapies, have been introduced and, in part, approved for the treatment of TC harboring specific mutations. For example, selpercatinib and pralsetinib inhibit mutant RET in medullary thyroid cancer but they can also block the RET fusion proteins-mediated signaling found in PTC. Entrectinib and larotrectinib, can be used in patients with progressive RAI-resistant TC harboring TRK fusion proteins. In addition FDA authorized the association of dabrafenib (BRAFV600E inhibitor) and trametinib (MEK inhibitor) for the treatment of BRAFV600E-mutated ATC. These drugs not only can limit the cancer spread, but in some circumstance they are able to induce the re-differentiation of aggressive tumors, which can be again submitted to new attempts of RAI therapy. In this review we explore the current knowledge on the genetic landscape of TC and its implication on the development of new precise therapeutic strategies.

show abstract

Section: Genetic Pathways and Epigenetic Mechanisms Implicated In Tc ...mentioning

confidence: 99%

Section: Molecular Driven Therapiesmentioning

confidence: 99%

Molecular features of aggressive thyroid cancer

et al. 2022

View full text Add to dashboard Cite

show abstract

“…As per current guidelines from the National Comprehensive Cancer Network (NCCN) [ 4 ] and consensus statement from the American Head and Neck Society Endocrine Surgery Section and International Thyroid Oncology group [ 7 ], only patients with progressive or symptomatic RAI-resistant thyroid cancer should be considered for medical therapy; that may be guided by genetic testing [ 8 ], such as BRAF V600E mutation (for BRAF &/or MEK inhibitor), RET fusion (for RET inhibitors), NTRK1/2 fusion (for NTRK inhibitors), or ALK fusion (for ALK inhibitor) [ 4 , 7 ]. Epigenetic testing has a role in diagnostics.…”

Section: Discussionmentioning

confidence: 99%

“…In differentiated thyroid cancer, the thyrocytes can pick up iodine and that is the rationale for post-surgical radio ablation with radioactive iodine (RAI) in select cases. For the RAI-refractory differentiated thyroid cancers, the multikinase or tyrosine kinase inhibitors may be used [ 4 , 5 , 6 , 7 , 8 ]. The activity of these multikinase inhibitors is not linked to specific genomic changes and may be related to the anti-angiogenic effects of these drugs.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Association of DNA Promoter Methylation and BRAF Mutation in Thyroid Cancer

et al. 2023

View full text Add to dashboard Cite

The BRAF V600E mutation and DNA promoter methylation play important roles in the pathogenesis of thyroid cancer (TC). However, the association of these genetic and epigenetic alterations is not clear. In this study, using paired tumor and surrounding normal tissue from the same patients, on a genome-wide scale we tried to identify (a) any association between BRAF mutation and DNA promoter methylation, and (b) if the molecular findings may provide a basis for therapeutic intervention. We included 40 patients with TC (female = 28, male = 12) without distant metastasis. BRAF mutation was present in 18 cases. We identified groups of differentially methylated loci (DML) that are found in (a) both BRAF mutant and wild type, (b) only in BRAF mutant tumors, and (c) only in BRAF wild type. BRAF mutation-specific promoter loci were more frequently hypomethylated, whereas BRAF wild-type-specific loci were more frequently hypermethylated. Common DML were enriched in cancer-related pathways, including the mismatch repair pathway and Wnt-signaling pathway. Wild-type-specific DML were enriched in RAS signaling. Methylation status of checkpoint signaling genes, as well as the T-cell inflamed genes, indicated an opportunity for the potential use of PDL1 inhibitors in BRAF mutant TC. Our study shows an association between BRAF mutation and methylation in TC that may have biological significance.

show abstract

Significance of FNAC, BRAF mutation, and intraoperative frozen section in surgical decision‐making of thyroid nodules

Zhu

Chen

et al. 2023

Diagnostic Cytopathology

View full text Add to dashboard Cite

Background A preoperative method is desired to discriminate benign from malignant thyroid nodules. This retrospective study evaluated the diagnostic performance of BRAF (B‐Raf proto‐oncogene) mutation (BRAFV600E) positivity and fine‐needle aspiration cytology (FNAC) relative to intraoperative frozen section pathology. Methods Patients underwent preoperative FNAC of thyroid nodules. Cytology specimens were classified according to the Bethesda System for Reporting Thyroid Cytopathology (BSRTC), and analyzed for BRAFV600E using an amplification‐refractory mutation system (ARMS). Thyroid tissue was surgically removed and frozen sections processed for histology. The sensitivities and specificities of each analysis were compared, alone and in combination. Results Among 346 patients, 333/358 FNACs (93%) showed malignant nodules; 322 (93%) patients received a pathological diagnosis of papillary thyroid carcinoma (PTC). The sensitivity and specificity of BSRTC VI for malignancy was the highest among the BSRTC categories. Compared with FNAC, the BRAFV600E analysis had significantly higher sensitivity and specificity. The diagnostic efficacy of frozen section pathology was significantly higher than that of either BSRTC category or BRAFV600E analysis alone. Combining methods variably improved diagnostic performance. BRAFV600E was not associated with capsule infiltration, neurovascular infiltration, mono‐ or multifocal PTC, lymph node metastasis, or clinical stage. Conclusion The diagnostic performance of preoperative BRAFV600E determination was better than that of the BSRTC‐FNAC category; combining both improved sensitivity and specificity. Patients with positive malignancy scores from both should be recommended for surgery; those with negative scores require close monitoring. Surgical treatment should include comprehensive intraoperative frozen section assessment. BRAF mutations cannot indicate aggressive treatment.

show abstract

Molecular testing in thyroid cancer diagnosis and management

Cited by 13 publications

References 115 publications

Molecular features of aggressive thyroid cancer

Molecular features of aggressive thyroid cancer

Association of DNA Promoter Methylation and BRAF Mutation in Thyroid Cancer

Significance of FNAC, BRAF mutation, and intraoperative frozen section in surgical decision‐making of thyroid nodules

Contact Info

Product

Resources

About