Molecular Nodal Restaging Based on CEACAM5, FGFR2b and PTPN11 Expression Adds No Relevant Clinical Information in Resected Non-Small Cell Lung Cancer
Ivan Macia 1, Gemma Aiza 2, Ricard Ramos 1, Ignacio Escobar 3, Francisco Rivas 3, Anna Ureña 3, Samantha Aso 4, Gabriela Rosado 3, Pau Rodriguez-Taboada 3, Carlos Deniz 3, Ernest Nadal 5 6, Gabriel Capella 6 7
Abstract
Background:
Non-small cell lung cancer (NSCLC) has a high relapse rate, even in cases classified as localized disease. This suggests that conventional pathological staging may lack the sensitivity to detect micrometastatic disease in resected lymph nodes. This study aimed to evaluate the prognostic significance of embryonic molecular marker expression in histologically negative lymph nodes from patients with completely resected NSCLC.
Methods:
A total of 76 patients with completely resected NSCLC were included: 60 were classified as pN0 and 16 as pN1. A total of 347 lymph nodes and the corresponding primary tumors were analyzed. Expression levels of CEACAM5, FGFR2b, and PTPN11 were quantified by real-time RT-qPCR. Statistical analyses included the Kruskal-Wallis test, Kaplan-Meier survival curves, and log-rank tests.
Results:
High CEACAM5 expression was detected in 90 lymph nodes (26%). Based on molecular findings, 37 pN0 patients (62%) were reclassified as molecular N1 or N2, and 5 pN1 cases (31%) were upgraded to molecular N2. Interestingly, patients with molecular-positive nodes showed improved overall survival (OS; p = 0.04). FGFR2b overexpression was found in 41 lymph nodes (12%), leading to molecular restaging in 17 patients (22%). A trend toward better disease-free survival (DFS) was observed in these restaged patients (p = 0.09). In line with this, high Alofanib expression of CEACAM5 or FGFR2b in the primary tumors was associated with improved DFS (p = 0.06 and p < 0.02, respectively).
Conclusion:
Molecular restaging of lymph nodes using CEACAM5 and/or FGFR2b expression does not provide clinically relevant prognostic information beyond conventional pathological staging in NSCLC. This may be due to the association of their overexpression in primary tumors with more favorable outcomes.