High frequency of KRAS and EGFR mutation profiles in BRAF-negative thyroid carcinomas in Indonesia

Heriyanto, Didik Setyo; Laiman, Vincent; Limantara, Nikko Vanda; Anantawikrama, Widyan Putra Ana; Yuliani, Fara Silvia; Cempaka, Rita; Anwar, Sumadi Lukman

doi:10.1186/s13104-022-06260-4

Cited by 4 publications

(9 citation statements)

References 27 publications

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“…The FTC may not be I-131 avid and therefore resistant to radioactive treatment. Resistance to I-131 is likely in patients who have metastatic disease [ 3 , 47 , 95 , 99 , 132 , 135 , 136 , 139 , 140 , 141 , 142 ]. Around 10% of TC cancers are under-staged and deemed low-risk, not needing I-131 ablation or adjuvant therapy).…”

Section: Diagnosis and Management Of Follicular Carcinomamentioning

confidence: 99%

“…Follicular thyroid carcinoma may acquire aggressive mutations as it progresses. Some of the aggressive mutations that the FTC can acquire include TP53, TERT, and PI3K/AKT/mTOR mutations [ 3 , 6 , 9 , 47 , 61 , 98 , 99 , 132 , 163 , 164 ].…”

Section: Diagnosis and Management Of Follicular Carcinomamentioning

confidence: 99%

“…The effects of the mutations or re-arrangements on the pathways may include the initiation of the tumor, proliferation, failure of apoptosis, neovascularization, neo-lymphogenesis, neurogenesis, epithelial to mesenchymal differentiation, and acquisition of metastatic potential [ 9 ]. The genetic aberrations are usually mutually exclusive but may rarely occur in combination [ 47 , 83 ]. Changes in the manifestations of a gene may also occur with or without mutation and be driven by epigenetic alterations.…”

Section: Recent Development In the Genomics Of Follicular Carcinoma A...mentioning

confidence: 99%

“…The other factors that are important in the risk stratification of a patient who has FTC are the existence lymph node or systemic metastasis, pre-operative level of thyroglobulin (Tg) and completeness of surgical excision. The histological subtype, tumour differentiation of the tumour, immunohistochemistry, genomics, epigenomics, metabolomics and the changes in the micro-environment of the tumour also have an influence on the prognosis of WDTC and therefore guide of appropriate treatment [ 26 , 27 , 28 , 41 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ]. Additional markers that have been found to be useful in the risk stratification of patients with TC include serum Vitamin D and the neutrophil-to-lymphocyte ratio (NLR) [ 52 , 53 ].…”

Section: Introductionmentioning

confidence: 99%

“…Follicular thyroid carcinoma cannot be diagnosed pre-operatively on FNAC because it can be confused with a follicular adenoma, rarely spread to lymph nodes, and has a different mutational landscape from that of PTC [ 9 , 25 , 47 , 63 ]. Additionally, FTC has a higher tendency, when compared with PTC and other thyroid malignancies, to present with systemic metastases from an occult primary tumor [ 57 , 64 , 65 ].…”

Section: Introductionmentioning

confidence: 99%

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Multi-Omics and Management of Follicular Carcinoma of the Thyroid

et al. 2023

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Follicular thyroid carcinoma (FTC) is the second most common cancer of the thyroid gland, accounting for up to 20% of all primary malignant tumors in iodine-replete areas. The diagnostic work-up, staging, risk stratification, management, and follow-up strategies in patients who have FTC are modeled after those of papillary thyroid carcinoma (PTC), even though FTC is more aggressive. FTC has a greater propensity for haematogenous metastasis than PTC. Furthermore, FTC is a phenotypically and genotypically heterogeneous disease. The diagnosis and identification of markers of an aggressive FTC depend on the expertise and thoroughness of pathologists during histopathological analysis. An untreated or metastatic FTC is likely to de-differentiate and become poorly differentiated or undifferentiated and resistant to standard treatment. While thyroid lobectomy is adequate for the treatment of selected patients who have low-risk FTC, it is not advisable for patients whose tumor is larger than 4 cm in diameter or has extensive extra-thyroidal extension. Lobectomy is also not adequate for tumors that have aggressive mutations. Although the prognosis for over 80% of PTC and FTC is good, nearly 20% of the tumors behave aggressively. The introduction of radiomics, pathomics, genomics, transcriptomics, metabolomics, and liquid biopsy have led to improvements in the understanding of tumorigenesis, progression, treatment response, and prognostication of thyroid cancer. The article reviews the challenges that are encountered during the diagnostic work-up, staging, risk stratification, management, and follow-up of patients who have FTC. How the application of multi-omics can strengthen decision-making during the management of follicular carcinoma is also discussed.

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Section: Diagnosis and Management Of Follicular Carcinomamentioning

confidence: 99%

Section: Diagnosis and Management Of Follicular Carcinomamentioning

confidence: 99%

Section: Recent Development In the Genomics Of Follicular Carcinoma A...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Multi-Omics and Management of Follicular Carcinoma of the Thyroid

et al. 2023

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Prognostic prediction of patients having classical papillary thyroid carcinoma with a 4 mRNA-based risk model

Xiang,

Zhao,

Tang

et al. 2024

Medicine

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The dysregulation of protein-coding genes involved in various biological functions is closely associated with the progression of thyroid cancer. This study aimed to investigate the effects of dysregulated gene expressions on the prognosis of classical papillary thyroid carcinoma (cPTC). Using expression profiling datasets from the Cancer Genome Atlas (TCGA) database, we performed differential expression analysis to identify differentially expressed genes (DEGs). Cox regression and Kaplan–Meier analysis were used to identify DEGs, which were used to construct a risk model to predict the prognosis of cPTC patients. Functional enrichment analysis unveiled the potential significance of co-expressed protein-encoding genes in tumors. We identified 4 DEGs (SALL3, PPBP, MYH1, and SYNDIG1), which were used to construct a risk model to predict the prognosis of cPTC patients. These 4 genes were independent of clinical parameters and could be functional in cPTC carcinogenesis. Furthermore, PPBP exhibited a strong correlation with poorer overall survival (OS) in the advanced stage of the disease. This study suggests that the 4-gene signature could be an independent prognostic biomarker to improve prognosis prediction in cPTC patients older than 46.

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Profile of BRAFV600E, BRAFK601E, NRAS, HRAS, and KRAS Mutational Status, and Clinicopathological Characteristics of Papillary Thyroid Carcinoma in Indonesian National Referral Hospital

Harahap,

Subekti,

Panigoro

et al. 2023

TACG

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Introduction BRAF V600E and RAS mutations are the most common gene mutations in papillary thyroid carcinoma (PTC) that may be correlated with its biological behavior. There are still limited data about BRAF V600E and RAS mutations in Indonesia. This study aims to determine the prevalence of BRAF V600E and RAS mutations, and their association with clinicopathologic characteristics. Methods Patients who had total thyroidectomy from 2019 to 2021 and those who met our study criteria underwent PCR and DNA sequencing analysis for BRAF V600E, BRAF K601E, exon 2 and 3 of NRAS, HRAS , and KRAS . Analyses were performed to determine the associations of BRAF V600E and RAS mutations with clinicopathologic characteristics. Results Of 172 PTC patients, BRAF V600E mutation was observed in 37.8% of the patients and RAS mutations were found in 21.5%. One patient harbored BRAF K601E mutation. There was a significant association of BRAF V600E with a high-stage (p = 0.033, OR: 3.279; 95% CI: 1.048–10.259), tall-cell variants (p ≤0.001, OR: 41.143; 95% CI: 11.979–141.308), non-encapsulated (p = 0.001, OR: 4.176; 95% CI: 2.008–8.685), lymphovascular invasion (p = 0.043, OR: 1.912; 95% CI: 1.018–3.592), extrathyroidal extension (p = <0.001, OR: 3.983; 95% CI: 1.970–8.054), and lymph node metastasis (p = 0.009, OR: 2.301; 95% CI: 1.224–4.326). Follicular variant (p = 0.001, OR: 7.011; 95% CI: 2.690–18.268), encapsulated (p = 0.017, OR: 2.433; 95% CI: 1.161–5.100), and absent of extrathyroidal extension (p = 0.033, OR: 2.890; 95% CI: 1.052–7.940) were associated with RAS mutations. Conclusion A significant association between BRAF V600E mutation and high clinical stage, tall-cell variants, non-encapsulated morphology, lymphovascular invasion, extrathyroidal extension, and lymph node metastasis in PTC was observed. RAS mutations were associated with the follicular variant, encapsulated tumor, and no extrathyroidal extension. HRAS -mutated PTC frequently exhibited tumor multifocality.

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High frequency of KRAS and EGFR mutation profiles in BRAF-negative thyroid carcinomas in Indonesia

Cited by 4 publications

References 27 publications

Multi-Omics and Management of Follicular Carcinoma of the Thyroid

Multi-Omics and Management of Follicular Carcinoma of the Thyroid

Prognostic prediction of patients having classical papillary thyroid carcinoma with a 4 mRNA-based risk model

Profile of BRAFV600E, BRAFK601E, NRAS, HRAS, and KRAS Mutational Status, and Clinicopathological Characteristics of Papillary Thyroid Carcinoma in Indonesian National Referral Hospital

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