Cancer Res Treat.  2017 Oct;49(4):906-914. 10.4143/crt.2016.424.

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

Affiliations
  • 1Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. silkahn@skku.edu
  • 2Samsung Biomedical Research Institute, Seoul, Korea.
  • 3Department of Pathology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea.
  • 4Department of Otorhinolaryngology-Head and Neck Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

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.

Keyword

Papillary thyroid carcinoma; BRAF; PIK3CA; RET

MeSH Terms

Gene Fusion
Humans
Retrospective Studies
Sequence Analysis, DNA
Thyroid Gland*
Thyroid Neoplasms*

Figure

  • Fig. 1. Kaplan-Meier curves of relapse-free survival according to tumor stage and risk stratification. (A) Relapse-free survival of papillary thyroid carcinoma (PTC) patients according to American Joint Committee on Caner/Tumor-Nodes-Metastasis (AJCC/TNM) stage. (B) Relapse-free survival of PTC patients according to American Thyroid Association risk stratification.

  • Fig. 2. Mutations and fusions in high-risk papillary thyroid carcinoma. Heatmap of mutations (A) and fusions (B) found in 240 papillary thyroid carcinoma samples. The percentage of mutation and fusion incidence is noted at the left. The horizontal axis represents the complete dataset of patients. AJCC, American Joint Committee on Cancer; ATA, American Thyroid Association.

  • Fig. 3. Impact of genetic alteration pattern on survival. (A) Relapse-free survival. (B) Overall survival. A Kaplan-Meier curve is presented according to the presence or absence of genetic alterations. Statistical analysis revealed no difference in recurrence-free probability among patients with no genetic alteration, one genetic alteration, two genetic alterations, or three genetic alterations.


Reference

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