Genetic Determinants for Prediction of Outcome of Patients with Papillary Thyroid Carcinoma

BackgroundPapillary thyroid microcarcinomas (PTMCs) have been attributed to the recent increased incidence of thyroid cancer. Although indolent, a subset of PTMC could potentially develop distant metastasis (DM). This study aimed to evaluate the clinico-pathological features and molecular characteristics of PTMC and identify the risk factors for DM in PTMC patients from Middle Eastern ethnicity.MethodsWe retrospectively analyzed 210 patients with histologically confirmed PTMC. Clinico-pathological associations for DM, BRAF mutation and TERT mutation were analyzed successfully in 184 patients. Multivariate analysis was performed using Cox proportional hazards model and logistic regression analysis.ResultsAmong the PTMC patients included in this cohort, DM was noted in 6.0% (11/184), whereas tumor relapse occurred in 29/184 (15.8%). Of the 11 cases with DM, lung metastasis occurred in 8 cases, bone metastasis in 2 cases and brain metastasis in 1 case. Presence of extrathyroidal extension and male sex were significantly associated with DM. Molecular analysis showed BRAF V600E mutations to be the most frequent, being detected in 45.7% (84/184). TERT promoter mutations were detected in 16 (8.7%) cases and were significantly associated with DM and shorter metastasis-free survival in multivariate analysis.ConclusionsOur study indicates a surprisingly high frequency of TERT promoter mutation in Saudi patients with PTMC. Identifying TERT promoter mutations as an independent predictor of DM in patients with microcarcinoma could explain the inherent aggressive nature of PTMC from Middle Eastern ethnicity and magnify its role in patient risk stratification, which might help in improving therapeutic strategy for these patients.

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“…Studies by Povoa et al. ( 60 ) and Melo et al. ( 61 ) analyzed the association of TERT and BRAF mutations with distant metastasis in PTC.…”

Section: Discussionmentioning

confidence: 99%

“…Similar findings have been reported in PTC by Melo et al(58) and others(37,55,59), where they show that TERT promoter mutations are a marker for DM. Studies by Povoa et al(60) andMelo et al (…”

mentioning

confidence: 95%

TERT Promoter Mutations Are an Independent Predictor of Distant Metastasis in Middle Eastern Papillary Thyroid Microcarcinoma

et al. 2022

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“…On the contrary, Povoa et al and Xing et al found no relation between mutation and poorer prognosis. Most patients with RAS mutation alone had a stage I diagnosis, usually presenting excellent responses to therapy, and were free of disease at the end of follow-up [ 42 , 43 ].…”

Section: Genetic Aberrations Markersmentioning

confidence: 99%

Can We Predict Differentiated Thyroid Cancer Behavior? Role of Genetic and Molecular Markers

et al. 2021

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Thyroid cancer is ranked in ninth place among all the newly diagnosed cancer cases in 2020. Differentiated thyroid cancer behavior can vary from indolent to extremely aggressive. Currently, predictions of cancer prognosis are mainly based on clinicopathological features, which are direct consequences of cell and tissue microenvironment alterations. These alterations include genetic changes, cell cycle disorders, estrogen receptor expression abnormalities, enhanced epithelial-mesenchymal transition, extracellular matrix degradation, increased hypoxia, and consecutive neovascularization. All these processes are represented by specific genetic and molecular markers, which can further predict thyroid cancer development, progression, and prognosis. In conclusion, evaluation of cancer genetic and molecular patterns, in addition to clinicopathological features, can contribute to the identification of patients with a potentially worse prognosis. It is essential since it plays a crucial role in decision-making regarding initial surgery, postoperative treatment, and follow-up. To date, there is a large diversity in methodologies used in different studies, frequently leading to contradictory results. To evaluate the true significance of predictive markers, more comparable studies should be conducted.

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“…On genetic analysis, the occurrence of BRAF and RAS mutations are uncommon events in DSVPTC and activation of RET/PTC rearrangements are common (9). Genetic detection is not only crucial to the diagnosis for PTC, and also used to assess the prognosis (10,11). When the morphology is atypical, genetic detection can be of great help to pathologists.…”

Section: Introductionmentioning

confidence: 99%

Atypical Papillary Thyroid Carcinoma with Squamous Metaplasia and RET/NRAS/TERT/PIK3CA Mutations: A Case Report

Huang

Guo

et al. 2021

Preprint

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Background: Papillary thyroid carcinoma (PTC) with squamous metaplasia is a relatively rare and special subtype adenocarcinoma of thyroid which involves multiple genetic changes. We reported a rare case of atypical PTC with squamous metaplasia and RET/NRAS/TERT/PIK3CA mutations which was confirmed after surgical resection pathologically. Case summary: A 2.5×2.5×2 cm3, smooth, hard, clear boundaries and solid nodule on the left thyroid gland was found on relevant physical examination of the patient. And then, the unilateral radical resection of thyroid carcinoma was performed after diagnosing. The tumor cells were squamous metaplasia and arranged in structures with diffuse growth pattern microscopically. At high magnification, stretched nucleus, nuclear grooves and internuclear pseudoinclusions in tumor cells were detected, and the follicular epithelium cells were atypical. Immunohistochemical staining shown strong positiveness of CK19, TTF-1, P40 and Galectin-3, partial positiveness of TG of tumor cells and negativeness of Calcitonin, which could exclude medullary thyroid carcinoma (MTC). Furthermore, first generation sequencing of 18 PTC related genes techniques shown RET, NRAS, TERT and PIK3CA was mutated. Conclusion: Genetic detection is vital to the diagnosis of thyroid adenocarcinoma, especially for the PTC with atypical morphology or rare metaplasia

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Genetic Determinants for Prediction of Outcome of Patients with Papillary Thyroid Carcinoma

Cited by 24 publications

References 66 publications

TERT Promoter Mutations Are an Independent Predictor of Distant Metastasis in Middle Eastern Papillary Thyroid Microcarcinoma

TERT Promoter Mutations Are an Independent Predictor of Distant Metastasis in Middle Eastern Papillary Thyroid Microcarcinoma

Can We Predict Differentiated Thyroid Cancer Behavior? Role of Genetic and Molecular Markers

Atypical Papillary Thyroid Carcinoma with Squamous Metaplasia and RET/NRAS/TERT/PIK3CA Mutations: A Case Report

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