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Genetic Alterations and Their Clinical Implications in High-Recurrence Risk Papillary Thyroid Cancer.

ABSTRACT: PURPOSE:Papillary thyroid carcinomas (PTCs) frequently involve genetic alterations. The objective of this study was to investigate genetic alterations and further explore the relationships between these genetic alterations and clinicopathological characteristics in a high-recurrence risk (node positive, N1) PTC group. MATERIALS AND METHODS:Tumor tissue blocks were obtained from 240 surgically resected patients with histologically confirmed stage III/IV (pT3/4 or N1) PTCs. We screened gene fusions using NanoString's nCounter technology and mutational analysis was performed by direct DNA sequencing. Data describing the clinicopathological characteristics and clinical courses were retrospectively collected. RESULTS:Of the 240 PTC patients, 207 (86.3%) had at least one genetic alteration, including BRAF mutation in 190 patients (79.2%), PIK3CA mutation in 25 patients (10.4%), NTRK1/3 fusion in six patients (2.5%), and RET fusion in 24 patients (10.0%). Concomitant presence of more than two genetic alterations was seen in 36 patients (15%). PTCs harboring BRAF mutation were associated with RET wild-type expression (p=0.001). RET fusion genes have been found to occur with significantly higher frequency in N1b stage patients (p=0.003) or groups of patients aged 45 years or older (p=0.031); however, no significant correlation was found between other genetic alterations. There was no trend toward favorable recurrence-free survival or overall survival among patients lacking genetic alterations. CONCLUSION:In the selected high-recurrence risk PTC group, most patients had more than one genetic alteration. However, these known alterations could not entirely account for clinicopathological features of high-recurrence risk PTC.

SUBMITTER: Lee MY

PROVIDER: S-EPMC5654158 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Genetic Alterations and Their Clinical Implications in High-Recurrence Risk Papillary Thyroid Cancer.

Lee Min-Young MY Ku Bo Mi BM Kim Hae Su HS Lee Ji Yun JY Lim Sung Hee SH Sun Jong-Mu JM Lee Se-Hoon SH Park Keunchil K Oh Young Lyun YL Hong Mineui M Jeong Han-Sin HS Son Young-Ik YI Baek Chung-Hwan CH Ahn Myung-Ju MJ

Cancer research and treatment 20161226 4

<h4>Purpose</h4>Papillary thyroid carcinomas (PTCs) frequently involve genetic alterations. The objective of this study was to investigate genetic alterations and further explore the relationships between these genetic alterations and clinicopathological characteristics in a high-recurrence risk (node positive, N1) PTC group.<h4>Materials and methods</h4>Tumor tissue blocks were obtained from 240 surgically resected patients with histologically confirmed stage III/IV (pT3/4 or N1) PTCs. We scree ...[more]

PMID: 28052655

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Project description:BackgroundCurrently, less aggressive treatment or even active surveillance of papillary thyroid microcarcinoma (PTMC) is widely accepted and recommended as a therapeutic management option. However, there are some concerns about these approaches. We investigated whether there are any demographic, clinical and ultrasound characteristics of PTMC patients that are easy to obtain and clinically available before surgery to help clinicians make proper therapeutic decisions.MethodsWe performed a retrospective chart review of 5,021 patients with thyroid tumors surgically treated in one center in 2008-2018. Finally, 182 (3.62%) PTMC patients were selected (158 (86.8%) females and 24 (13.2%) males, mean age 48.8±15.4 years). We analyzed the disease-free survival (DFS) time of the PTMC patients according to demographic and histopathological parameters. Univariate and multivariate logistic regression analyses were used to assess the relationships of demographic, clinical and ultrasound characteristics with aggressive histopathological features.ResultsAge ≥55 years, hypoechogenicity, microcalcifications, irregular tumor shape, smooth margins and high vascularity significantly increased the risk for minimal extrathyroidal extension (minETE), lymph node metastasis (LNM), and capsular and vascular invasion (p<0.0001). Multivariate logistic regression analysis demonstrated a statistically significant risk of LNM (OR = 5.98, 95% CI: 2.32-15.38, p = 0.0002) and trends toward significantly higher rates of minETE and capsular and vascular invasion (OR = 2.24, 95% CI: 0.97-5.19, p = 0.056) in patients ≥55 years than in their younger counterparts. The DFS time was significantly shorter in patients ≥55 years (p = 0.015), patients with minETE and capsular and vascular invasion (p = 0.001 for all), patients with tumor size >5 mm (p = 0.021), and patients with LNM (p = 0.002).ConclusionsThe absence of microcalcifications, irregular tumor shape, blunt margins, hypoechogenicity and high vascularity in PTMC patients below 55 years and with tumor diameters below 5 mm may allow clinicians to select individuals with a low risk of local recurrence so that they can receive less aggressive management.

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Genetic Alterations and Their Clinical Implications in High-Recurrence Risk Papillary Thyroid Cancer.

Publications

Genetic Alterations and Their Clinical Implications in High-Recurrence Risk Papillary Thyroid Cancer.

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