Significance of RAS Mutations in Thyroid Benign Nodules and Non-Medullary Thyroid Cancer

Marotta, Vincenzo; Bifulco, Maurizio; Vitale, Mario

doi:10.3390/cancers13153785

Cited by 52 publications

(39 citation statements)

References 106 publications

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“…On the contrary, limited data are available for comparisons of the molecular behavior of thyroid nodules with benign cytology. 13 In this study, on histologic examination, 16 cases were classified as neoplastic, and 35 were classified as nonneoplastic. The majority of the nonneoplastic cases (>50%) were characterized as adenomatoid nodules.…”

Section: Discussionmentioning

confidence: 99%

RAS mutation and associated risk of malignancy in the thyroid gland: An FNA study with cytology‐histology correlation

Gilani

Abi‐Raad

Garritano

et al. 2021

Cancer Cytopathology

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Background Activating point mutations of the RAS gene (NRAS, HRAS, and KRAS) can be seen in benign and malignant thyroid tumors; among these, NRAS mutations are more commonly seen. This study was conducted to evaluate the thyroid risk of malignancy (ROM) associated with RAS mutations in thyroid fine‐needle aspiration (FNA) at the authors' institution. Methods The authors searched their electronic database system between January 2015 and May 2021 for thyroid FNA cases with any type of RAS mutation. Molecular alterations were identified with the ThyroSeq Genomic Classifier, ThyGeNEXT (thyroid oncogene panel)/ThyraMIR (miRNA classifier), or ThyroSure gene panel. Results A total of 127 cases (age, 51 ± 14 years; 100 females and 27 males) were identified, and 72 had histologic follow‐up. The overall ROM associated with RAS mutations (with or without any other molecular alterations) was 29%, whereas the ROM was lower (18%) with RAS mutations only. Isolated NRAS, HRAS, and KRAS mutation–associated ROMs were 15%, 27%, and 14%, respectively. Among these RAS‐mutated cases, the cases with a Bethesda category IV cytologic diagnosis had a higher ROM than the cases with a category III diagnosis (38% vs 17%). Twenty‐one histologically confirmed malignant cases were mostly classified on cytology as category IV lesions (14 of 34; 41%), and the remainder were either category III (6 of 35; 17%) or V lesions (1 of 1; 100%). Conclusions This study demonstrated that the overall RAS mutation–associated ROM in thyroid FNA was intermediate (29%), and isolated HRAS mutations appeared to have a higher ROM (27%) than NRAS and KRAS mutations (15% and 14%, respectively).

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Section: Discussionmentioning

confidence: 99%

RAS mutation and associated risk of malignancy in the thyroid gland: An FNA study with cytology‐histology correlation

Gilani

Abi‐Raad

Garritano

et al. 2021

Cancer Cytopathology

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“…The utility of SP174 immunostaining in the differential diagnosis of follicular-patterned thyroid neoplasms is, however, limited due to a lack of specificity of RAS mutations. These are present at variable frequencies in non-neoplastic and neoplastic thyroid lesions, including hyperplastic thyroid nodule, FA, FTC, NIFTP, and the follicular variant of PTC [ 11 , 157 , 160 ]. RAS mutated colorectal carcinoma or melanoma cases can be used as positive control.…”

Section: Immunohistochemical Markersmentioning

confidence: 99%

Emerging Biomarkers in Thyroid Practice and Research

Agarwal

Bychkov

Jung

2021

Cancers

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Thyroid cancer is the most common endocrine malignancy. Recent developments in molecular biological techniques have led to a better understanding of the pathogenesis and clinical behavior of thyroid neoplasms. This has culminated in the updating of thyroid tumor classification, including the re-categorization of existing and introduction of new entities. In this review, we discuss various molecular biomarkers possessing diagnostic, prognostic, predictive and therapeutic roles in thyroid cancer. A comprehensive account of epigenetic dysregulation, including DNA methylation, the function of various microRNAs and long non-coding RNAs, germline mutations determining familial occurrence of medullary and non-medullary thyroid carcinoma, and single nucleotide polymorphisms predisposed to thyroid tumorigenesis has been provided. In addition to novel immunohistochemical markers, including those for neuroendocrine differentiation, and next-generation immunohistochemistry (BRAF V600E, RAS, TRK, and ALK), the relevance of well-established markers, such as Ki-67, in current clinical practice has also been discussed. A tumor microenvironment (PD-L1, CD markers) and its influence in predicting responses to immunotherapy in thyroid cancer and the expanding arena of techniques, including liquid biopsy based on circulating nucleic acids and plasma-derived exosomes as a non-invasive technique for patient management, are also summarized.

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“…Genetic changes in RAS family genes are considered as “early” alterations and are characteristic for DTCs, especially for FTC. However, mutations of downstream effectors of the pathway are also commonly identified in less-differentiated TCs [ 30 , 44 ].…”

Section: Introductionmentioning

confidence: 99%

“…Constitutively activated (mutated) GTP-bound RAS isoforms stimulate downstream effector pathways, even in the absence of extracellular stimuli ( Figure 2 ) [ 45 , 46 ]. The utility of RAS mutations as a diagnostic tool is rather low [ 44 ]. RAS mutations occur, on average, in 30–40% of FTCs, 30–45% of the follicular variant of PTCs (FVPTCs), in approximately 25% of ATCs and PDTCs, in 15% of HCCs and in 10–45% of MTCs.…”

Section: Introductionmentioning

confidence: 99%

Novel Inhibitor-Based Therapies for Thyroid Cancer—An Update

Ratajczak

Gawel

Godlewska

2021

IJMS

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Thyroid cancers (TCs) are the most common tumors of the endocrine system and a constant rise in the number of TC cases has been observed for the past few decades. TCs are one of the most frequent tumors in younger adults, especially in women, therefore early diagnosis and effective therapy are especially important. Ultrasonography examination followed by fine needle biopsy have become the gold standard for diagnosis of TCs, as these strategies allow for early-stage detection and aid accurate qualification for further procedures, including surgical treatment. Despite all the advancements in detection and treatment of TCs, constant mortality levels are still observed. Therefore, a novel generation line of targeted treatment strategies is being developed, including personalized therapies with kinase inhibitors. Recent molecular studies on TCs demonstrate that kinase inhibitor-based therapies might be considered as the most promising. In the past decade, new kinase inhibitors with different mechanisms of action have been reported and approved for clinical trials. This review presents an up-to-date picture of new approaches and challenges of inhibitor-based therapies in treatment of TCs, focusing on the latest findings reported over the past two years.

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Significance of RAS Mutations in Thyroid Benign Nodules and Non-Medullary Thyroid Cancer

Cited by 52 publications

References 106 publications

RAS mutation and associated risk of malignancy in the thyroid gland: An FNA study with cytology‐histology correlation

RAS mutation and associated risk of malignancy in the thyroid gland: An FNA study with cytology‐histology correlation

Emerging Biomarkers in Thyroid Practice and Research

Novel Inhibitor-Based Therapies for Thyroid Cancer—An Update

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