P2.13-04 Molecular Nodal Restaging Based on Embryonic Markers Expression Adds No Relevant Clinical Information in Resected Lung Cancer

Abstract

The relapse rate in non-small cell lung cancer (NSCLC) is high, even in localised disease, suggesting that the current approach to pathological staging is insufficiently sensitive to detect occult micrometastases present in resected lymph nodes. Therefore, we aimed to determine the prognostic value of the expression of embryonic molecular markers in histologically-negative lymph nodes of completely-resected NSCLC. 76 NSCLC patients undergoing radical resection were included. Primary tumours and 347 lymph nodes were studied. The molecular markers finally were selected based on testing of 27 normal lung and 129 lung tumour samples as well as 25 lymph nodes obtained from non-neoplastic diseases. CEACAM5, FGFR2b, and PTPN11 expression levels were evaluated through mRNA analysis using real-time RT-qPCR assay. Statistical analyses included the Kruskal-Wallis test, Kaplan Meier curves, and log-rank tests. CEACAM5 expression levels were scored as high in 90 lymph nodes (26%). The molecular-positive lymph nodes lead to the restaging of 37 (62%) pN0 patients as molecular N1 or N2 and 5 (31%) pN1 cases were reclassified as molecular-positive N2. Surprisingly, molecular-positive patients (42, 55%) associated with a better OS (overall survival, p=0,04) than molecular-negative patients (34, 45%). FGFR2b overexpression was observed in 41 (12%) lymph nodes leading to the restaging of 17 patients (22%). Again a trend was observed towards a better DFS (disease-free survival) in the restaged patients (p=0,09). PTPN11 expression levels were high in 109 (31%) lymph nodes and led to the restaging of 41 (54%) patients who did not correlate with clinical outcome (p=0,61). The combination of CEACAM5-FGFR2b restaged the same number of patients than CEACAM5 only. Accordingly, high expression levels of CEACAM5 or FGFR2b in the primary tumour were related to better DFS (p<0,06; p<0,02, respectively); PTPN11 did not correlate with prognosis (p=0,37). Molecular nodal restaging based on expression levels of CEACAM5 and/or FGFR2b, does not add relevant clinical information to pathological staging of NSCLC likely related to the better prognosis of their overexpression in primary tumors.