Clinical and Oncological Features of Children and Young Adults with Multiple Endocrine Neoplasia Type 2A

Puñales, Márcia Khaled; Rocha, Andreia Possatti da; Meotti, Carolina Degen; Gross, Jorge Luiz; Maia, Ana Luiza

doi:10.1089/thy.2007.0414

Cited by 36 publications

(21 citation statements)

References 35 publications

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“…Clinical and laboratory data were collected for each individual. Patients underwent a complete clinical examination, and laboratory tests were performed as described previously (9,26). The control group was composed of 308 unrelated cancerunaffected volunteers attending the blood donation facility of our Institution.…”

Section: Patientsmentioning

confidence: 99%

Additive effect of RET polymorphisms on sporadic medullary thyroid carcinoma susceptibility and tumor aggressiveness

Ceolin

Siqueira²,

Ferreira³

et al. 2012

European Journal of Endocrinology

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Objective: RET single nucleotide polymorphisms (SNPs) have been implicated in the pathogenesis and progression of medullary thyroid carcinoma (MTC). Here, we investigated the influence of multiple RET variants (G691S, L769L, S836S, and S904S) on the risk of MTC and tumor behavior. Design and methods: One hundred and seven MTC patients and 308 cancer-unaffected control individuals were included. SNPs were analyzed using Custom TaqMan Genotyping Assays. Haplotypes based on the combination of allelic variants were inferred using a Bayesian statistical method. Results: The minor allele frequencies in MTC patients were as follows: L769L: 28.0%, S836S: 8.9%, and G691S/S904S: 22.2%. The RET L769L and S836S SNPs were associated with increased risk of MTC (odds ratio (OR)Z1.95, 95% CI: 1.2-3.1, PZ0.005 and ORZ2.29, 95% CI: 1.2-4.5, PZ0.017 respectively). The adjusted OR for individuals harboring haplotypes with three or more polymorphic alleles was 3.79 (95% CI: 1.5-9.5; PZ0.004), indicating an additive effect of these variants on the risk for MTC. Among MTC patients, no significant associations were observed between RET variants and age of diagnosis or tumor size but serum calcitonin levels increased according to the number of risk alleles (PZ0.003). Remarkably, patients carrying haplotypes with three or four risk alleles had increased risk for lymph node and distant metastases at diagnosis (ORZ5.84, 95% CI: 1.1-31.2, PZ0.039). Further analysis using Kaplan-Meier model demonstrated that metastatic disease occurred earlier in individuals harboring multiple risk alleles. Conclusion: Our results demonstrated an additive effect of RET polymorphic alleles on the estimated risk of developing aggressive MTC.

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Section: Patientsmentioning

confidence: 99%

Additive effect of RET polymorphisms on sporadic medullary thyroid carcinoma susceptibility and tumor aggressiveness

Ceolin

Siqueira²,

Ferreira³

et al. 2012

European Journal of Endocrinology

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“…The RET proto-oncogene is the susceptibility gene for hereditary MTC, and recent studies showed a timedependent MTC progression, strengthening the importance of a DNA-based RET genotype analysis for the identification of asymptomatic gene carriers at risk of developing MTC (Machens et al 2003, Punales et al 2008. Gain-of-function germline mutations in MEN 2A…”

Section: Introductionmentioning

confidence: 96%

The RET polymorphic allele S836S is associated with early metastatic disease in patients with hereditary or sporadic medullary thyroid carcinoma

Siqueira

Romitti²,

Rocha³

et al. 2010

Endocrine-Related Cancer

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The possible role of RET variants in modifying the natural course of medullary thyroid carcinoma (MTC) is still a matter of debate. Here, we investigate whether the RET variants L769L, S836S, and G691S/S904S influence disease presentation in hereditary or sporadic MTC patients. One hundred and two patients with hereditary MTC and 81 patients with sporadic MTC attending our institution were evaluated. The frequencies of RET polymorphisms in hereditary MTC were as follows: L769L, 17.3%; S836S, 7.95%; and S904S/G691S, 18.2%. No associations were observed between these polymorphisms and pheochromocytoma, hyperparathyroidism, lymph node, or distant metastasis. However, patients harboring the S836S variant were younger than those without this allele (17G8.2 vs 28.6G14.4 years, PZ0.01), suggesting that these patients had metastases at a young age. Accordingly, the cumulative frequency of local and/or distant metastases as estimated by Kaplan-Meier curves showed that lymph node and distant metastases occurred earlier in patients harboring the S836S variant (PZ0.003 and PZ0.026 respectively). The S836S allele frequency was higher in sporadic MTC patients than in controls (10.5 vs 3.1%, PZ0.01). Individuals harboring the S836S variant were younger (38.6G13.3 vs 48.5G16.7 years, PZ0.02) and showed a higher percentage of lymph node and distant metastases (PZ0.02 and PZ0.04 respectively). Kaplan-Meier estimates of lymph node and distant metastases yielded distinct curves for patients with or without the S836S allele (PZ0.002 and PZ0.001 respectively). Additional analyses using a COX regression model showed that the S836S variant was independently associated with metastatic disease (hazard ratio 2.82 (95% confidence interval 1.51-5.26), PZ0.001). In conclusion, the RET S836S variant is associated with early onset and increased risk for metastatic disease in patients with hereditary or sporadic MTC.

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“…Literatürde benign sitolojiye sahip nodüller incelendiğinde >4 cm nodüllerde malignitenin kesin olarak ekartasyonu belirsizliğini korumaktadır. Bu hasta grubunda daha küçük boyutlu nodüllerden farklı tedavi yaklaşımları izlenebilir (KD 3) [33,34].…”

Section: Tiroid Nodüllerinde İi̇abunclassified

Tiroid nodüllerine güncel yaklaşım: “2015 ATA” ve “2016 AACE/ACE/AME” kılavuzları derlemesi

Şişik¹,

Başak²,

Köse³

2017

Archives of Clinical and Experimental Medicine

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Clinical importance of the thyroid nodules arises from their malign potential. There are guidelines from several different organizations to determine follow-up options and, if necessary, surgical treatment options for thyroid nodules. Among them, the guidelines created by ATA and AACE/ACE/AME are accepted in many centers of the world. This paper aims to present the current status of ultrasound and fine needle aspiration biopsy in thyroid nodules in the context of the literature according to the updated versions of these guidelines.

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Clinical and Oncological Features of Children and Young Adults with Multiple Endocrine Neoplasia Type 2A

Abstract: Our data show a time-dependent MTC progression. The presence of a palpable thyroid nodule and lymph node metastasis at diagnosis was associated with persistent or recurrent disease after surgical procedure.

Cited by 36 publications

References 35 publications

Additive effect of RET polymorphisms on sporadic medullary thyroid carcinoma susceptibility and tumor aggressiveness

Additive effect of RET polymorphisms on sporadic medullary thyroid carcinoma susceptibility and tumor aggressiveness

The RET polymorphic allele S836S is associated with early metastatic disease in patients with hereditary or sporadic medullary thyroid carcinoma

Tiroid nodüllerine güncel yaklaşım: “2015 ATA” ve “2016 AACE/ACE/AME” kılavuzları derlemesi

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