Endocrine Abstracts

JOINT1517

PTC is characterized by a relatively low frequency of somatic mutations compared to other carcinomas, with BRAF-mutant tumors being the most common. Gene fusions are present in 15% of PTCs. PTC is associated with a very good prognosis, there are infrequent cases of recurrent or metastatic disease that require systemic therapy targeted to tumor’s genomic characteristics. Given the risk of DNA degradation, genetic testing of paraffin-embedded tissue should ideally be performed as early as possible. High costs of these procedures make universal testing unfeasible. Patients who may benefit from genetic characterization of their tumor need to be preselected early, long before the tyrosine kinase inhibitors (TKI) therapy may be required. This is the preliminary study on selective genetic screening for targetable somatic mutations in PTC patients.

Material and Methods: Since mid-2022, we have performed next-generation sequencing (NGS) of tumor tissues from PTC patients with extensive nodal involvement, distant metastases, early recurrence, or requiring repeated surgeries. 40 such patients (15 M, 25 F, median age 45) were included. In each case, NGS was conducted to detect pathogenic variants of AKT1, ALK, BRAF, CTNNB1, DDR2, EGFR, ERBB2, FGFR1, GNAS, HRAS, IDH1, IDH2, KRAS, MAP2K1, MET, NRAS, PIK3CA, RET, ROS1 and fusions of ALK, AXL, BRAF, CCND1, EGFR, FGFR1, FGFR2, FGFR3, MET, NRG1, NTRK1, NTRK2, NTRK3, PPARG, RAF1, RET, ROS1, THADA. The analysed variables included age, tumor characteristics (TNM, extranodal extension), categorised lymph node metastases size, repeated surgery, and remission status at latest follow-up. Statistical analyses were performed using the Mann-Whitney U test for continuous variables, and Chi-square or Fisher’s exact tests for categorical variables.

Results: Among the 40 patients, 11 (27. 5%) were identified with gene fusions [CCDC6(1)-RET(12), NCOA(4)-RET(12), CCDC6(1)-RET(12), CCDC6(1)-RET(12), ETV6(4)-NTRK3(14), ERC1(17)-RET(12), TMEM9(5)-BRAF(9), NCO4(7)-RET(12), NCOA4(6)-RET(12), SQSTM1(5)-NTRK1(10)] (2 M, 9 F; median age 35). In the no-fusion group (13 M, 16 F, median age 47), BRAF V600E was found in 22 patients, in 6 cases no pathogenic variants were detected, one sample was degraded. The fusion-positive group was significantly younger (P = 0. 007). Lymph node metastases larger than 10 mm were more common in fusion-positive subjects (P = 0. 009). No other significant differences in clinical course of PTC were observed.

Conclusions: Younger PTC patients with massive lymph node involvement, especially larger nodes, should be prioritized when considering the genetic screening of tumor tissues. Early genetic testing in these patients may identify actionable mutations or fusions, enabling timely targeted therapies.