Actualities in Genetics of Differentiated Thyroid Cancer

Dobrescu, Ruxandra; Badiu, Corin

doi:10.4183/aeb.2020.118

Cited by 4 publications

(3 citation statements)

References 19 publications

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“…To determine the optimal surgical approach, and to decrease the need for unnecessary thyroidectomies, a new set of criteria should be established -but until then, we suggest the more frequent application of primary total thyroidectomy. Appending previously established predictive models with new features such as genetic and epigenetic data from FNA samples is one of the newly emerging promising methods [18][19][20][21][22].…”

Section: Discussionmentioning

confidence: 99%

Comparison of surgical strategies in the treatment of low-risk differentiated thyroid cancer

et al. 2023

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Context Increasing diagnostic sensitivity in the detection of thyroid cancer has led to uncertainties in the optimal surgical approach of the smaller, low risk tumors. Current ATA guidelines consider lobectomy safe between 1 and 4 cm, while ETA advocates for primary total thyroidectomy to avoid reoperation, as final risk stratification is based on the histological results. Objective Our aim was to compare the differences in outcomes that are potentially achievable with adherence to the different guidelines, and also to examine the predictive value of clinical parameters on the incidence of postoperative risk factors. Methods We performed a retrospective cohort database analysis to identify the different surgical outcomes (based on postoperative risk factors) using ATA and ETA guidelines; the hypothetical rate of completion thyroidectomy when ATA or ETA recommends lobectomy; the accuracy of our preoperative evaluation; the utility of preoperative findings in predicting the optimal surgical strategy using binary logistic regression. Results Out of 248 patients, 152 (ATA) and 23 (ETA) cases would have been recommended for initial lobectomy. Following the guidelines, a postoperative risk factor would have been present in 61.8, and 65.2% of the cases, respectively. Except for angioinvasion, tumor size was not a significant predictor for the presence of postoperative risk factors. Conclusion Current pre-operative criteria are inadequate to accurately determine the extent of initial surgery and our postoperative findings verify the frequent need for completion thyroidectomy using both guidelines. As a consequence, in the absence of effective pre-operative set of criteria, we advocate primary total thyroidectomy in most cases.

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Section: Discussionmentioning

confidence: 99%

Comparison of surgical strategies in the treatment of low-risk differentiated thyroid cancer

et al. 2023

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“…On the contrary, the most common genetic mutation in malignant thyroid cancer is BRAF. BRAF mutation is associated with higher levels of lymph node invasion, metastasis and mortality in papillary thyroid cancer 29–31 . BRAF mutation is however more sensitive than specific in determining patient mortality, as seen by the high population prevalence of BRAF compared to the overall low mortality from thyroid cancer 30 .…”

Section: Discussionmentioning

confidence: 99%

“…Traditionally, TERT and TP53 mutations predict aggressive behaviour amongst thyroid malignancies either independently or in combination with other alterations. TERT adds telomeres to the ends of chromosomes, thereby stabilising them, leading to uncontrolled cell proliferation 30 . TERT mutations are often seen in poorly differentiated thyroid cancers, and its presence is independently associated with increased mortality 29,31 .…”

Section: Discussionmentioning

confidence: 99%

Utility of mutational analysis for risk stratification of indeterminate thyroid nodules in a real‐world setting

Torrecillas

Sharma

Neuberger

et al. 2021

Clinical Endocrinology

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Objective American Thyroid Association (ATAn) 2015 guidelines recommend repeat fine‐needle aspiration with molecular marker profiling (MMP) or diagnostic lobectomy in thyroid nodules yielding atypia of unknown significance/follicular lesion of unknown significance (AUS/FLUS) or follicular neoplasm/suspicious for follicular neoplasm (FN/SFN) cytology. Our objective is to describe the molecular profiles and histological correlates of these cytologically indeterminate nodules (CIN) to aid risk stratification. Design Retrospective chart review. Patients Adults with CIN that underwent MMP from 2017 to 2020. Measurements Pearsons' χ2, Fisher's exact test, nonparametric testing and multiple regression analysis were performed. Results A total of 89 CIN underwent mutational analysis. Of 55% (n = 49) were Bethesda class III AUS/FLUS and 45% (n = 40) were Bethesda class IV FN/SFN. The US phenotype of a CIN was isoechoic (53%) or hypoechoic (32%) with well‐defined margins (98%), absence of calcifications (75%) and mildly increased internal vascularity (70%). A total of 84% and 87% of nodules were classified as mild/moderate or low/intermediate risk per the Thyroid Imaging Reporting and Data System and ATA classifications, respectively. Based on the Thyroseq patient management resource, 6.7% (n = 6) of nodules had a high predicted probability of cancer (≥95%), 41.6% (n = 37) were intermediate probability (40%–94%) and 51.7% (n = 46) were low probability (<40%). MMP revealed positive mutations in 45% (n = 40) of nodules, with 71% demonstrating RAS mutations. Of the nodules that underwent resection (n = 38), 39% (n = 15) had malignant pathology. Increasing the threshold to recommend surgical resection to a Thyroseq predicted probability of cancer to ≥50%, had a 100% sensitivity and 65% specificity for detecting malignant nodules (area under the ROC curve: 0.86). The positive predictive value was 37% and the negative predictive value was 100%. Conclusion US phenotypes of CIN nodules were variable and did not aid in differentiating malignant from benign nodules. Of the CIN nodules with a positive MMP, most were RAS and had a benign pathology. With the exception of high‐risk genetic markers for malignancy, the threshold to recommend surgical resection should be raised for CIN. Further studies to improve risk stratification in these nodules are required.

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Matrix metalloproteinase-9 (MMP-9) promoter -1562C/T functional polymorphism is associated with an increased risk to develop micropapillary thyroid carcinoma

Dobrescu

Schipor

Manda

et al. 2022

CBM

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BACKGROUND: Matrix metalloproteinase-9 (MMP-9) is an important mediator of tumor initiation and progression. The MMP-9 promoter -1562C/T functional polymorphism increases gene expression and was identified as a susceptibility factor for various cancers. OBJECTIVE: To evaluate the influence of the MMP-9 promoter genotype on the risk of developing papillary thyroid cancer (PTC) and to correlate cancer patient genotype with the clinical and pathological phenotype. METHODS: We evaluated 236 patients with nodular thyroid disease pre-thyroidectomy (119 benign disease, 117 PTC). Genomic DNA was isolated from whole blood and the MMP-9 -1562C/T genotype was evaluated by PCR-RFLP analysis. RESULTS: Genotype frequencies were in Hardy-Weinberg equilibrium for all groups. The T allele was significantly more frequent in cancer compared to benign disease (17.5% vs 10.1%), p= 0.019. Patients with the CT or CT+TT genotype had an increased risk of developing PTC, specifically micropapillary thyroid carcinoma (MPTC) (CT genotype: OR = 6.467, p= 0.00006; CT+TT: OR = 6.859, p= 0.00002), but not more advanced stages (CT: p= 0.094; CT+TT: p= 0.157). The -1562C/T genotype did not significantly correlate with tumor histological subtype, invasion or TNM stage. CONCLUSION: The MMP-9 -1562C/T functional polymorphism may indicate susceptibility to develop thyroid cancer, specifically intrathyroidal clinically non-relevant MPTC. This suggests that although this genotype might be a predisposing factor, other genetic/epigenetic events are needed for cancer progression.

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Actualities in Genetics of Differentiated Thyroid Cancer

Abstract: Genetics of cancer is a hot topic, an excellent example of translational medicine. Risk stratification, selection of cases for surgery in Bethesda categories 3 &4 FNAB are examples of the high impact of genetic evaluation in thyroid neoplasia.

Cited by 4 publications

References 19 publications

Comparison of surgical strategies in the treatment of low-risk differentiated thyroid cancer

Comparison of surgical strategies in the treatment of low-risk differentiated thyroid cancer

Utility of mutational analysis for risk stratification of indeterminate thyroid nodules in a real‐world setting

Matrix metalloproteinase-9 (MMP-9) promoter -1562C/T functional polymorphism is associated with an increased risk to develop micropapillary thyroid carcinoma

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