High concordance in molecular profiles between primary tumors and matched lymph node metastases in differentiated thyroid carcinoma: implications for clinical sample selection

Molecular concordance between primary tumors (PT) and matched lymph node metastases (LNM) in differentiated thyroid carcinoma (DTC) remains further clarified, and the impact of LNM timing has not been evaluated. This study focused on the concordance between PT and LNM in 63 PT-LNM pairs from 55 DTCs, using a 10-gene real-time PCR targeting BRAF V600E, NRAS , HRAS , KRAS , TERT promoter (TERTp), PIK3CA , RET , PPARG , NTRK1 , and NTRK3 . Concordance between PT and LNM was assessed using Cohen’s kappa and McNemar’s test. Pairs were stratified into synchronous (≤ 6 months, n = 41) and asynchronous (> 6 months, n = 22) subgroups to assess the impact of LNM timing. The overall molecular concordance rate between PT and LNM was 88.9% (56/63). RET showed 100% agreement (Kappa = 1.00), while BRAF V600E, TERT p, and NTRK3 demonstrated 92.1%, 98.4%, and 98.4% agreement (Kappa = 0.79–0.83). No NRAS , HRAS , KRAS , PIK3CA , PPARG , or NTRK1 alterations were detected. Discordant pairs accounted for 11.1% (7/63), of which 71.4% (5/7) were BRAF V600E detected only in the PT but not in the matched LNM. Concordance rates were comparable in synchronous (87.8%, 36/41) and asynchronous (90.9%, 20/22) groups. Our findings confirm high PT-LNM molecular concordance regardless of the timing of LNM occurence, which may help guide the genetic testing strategy.