Clinical value of gene mutations in patients with papillary thyroid carcinoma

Introduction: Thyroid carcinoma is the most common endocrine malignancy, of which papillary thyroid carcinoma (PTC) accounts for 85-90%. Based on catalogue of somatic mutations in cancer (COSMIC) database and thyroid carcinoma related genes reported in the literature, 77 genes including single nucleotide variations (SNVs), insertion-deletions (InDels), gene fusions and reference genes could be detected by thyroseq v2 next-generation sequencing assay. The purpose of this study was to evaluate the clinical value of 77 genetic tests for evaluation of susceptibility gene mutations in patients with PTC.

Methods: Seventy-eight patients histologically diagnosed as PTC and underwent iodine -131 treatment within 6 months after total were retrospectively included. Data collecting included the clinical features, thyroid stimulating hormone (TSH), stimulated thyroglobulin (sTg) before radioactive iodine-131 treatment, pathology, genetic test results, initial risk stratification and efficacy after radioactive iodine-131 treatment. The mean follow-up was (10.04±4.33) months. Stimulated TSH level was greater than 30mIU/L before iodine-131 treatment. And TSH and anti-thyroglobulin antibodies (TgAb) was less than 0.5IU/L and 200IU/mL respectively at the last follow-up for all patients. Surgical specimens were used for genetic test and the 8th edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) TNM staging system was applied.

Results: Seven-eight PTC patients (26 males and 52 females; mean age, 39.12±11.53) were studied. The ratio of gene mutations in PTC patients was 94.87%. There were no significant differences for T stage, N stage, clinic outcome and gene mutations (all p>0.05) between different gender and age (<55y and ≥55y). The level of BMI in the male group was higher than the female group (p=0.000). The recurrence risk was mainly intermediate and high risk respectively for male and female (p=0.041). The recurrence risk and TNM stage were significantly higher in <55y than ≥55y (p=0.013 and 0.000). The outcomes showed there were SNVs/InDels in 15 genes and 5 types of gene fusions for all patients, without significant differences with T stage, N stage, TNM stage, tumor size, recurrence risk and gene mutations (all p>0.05). There was a negative correlation between gene mutations and sTg.

Conclusions: For patients with PTC, there was high mutation rate and with high level of SNVs/InDels. Gene mutation was much more common in women with high recurrence risk and younger than 55y. But there was no correlation during different clinic outcomes and between malignant thyroid nodules and metastatic lymph nodes, which meant radioactive iodine-131 therapy was effective for PTC patients with high initial recurrence risk and gene mutations.