부산대학교 도서관

Background and hypothesis. Clinical staging methods for non-small cell lung cancer (NSCLC) do not adequately predict pathological staging. The anomalous expression of embryonic molecular markers in tumour tissue may have prognostic value in patients with NSCLC. In thoracic lymph nodes, expression of these markers may indicate the presence of cancer cells and thus improve staging. Objectives. To determine agreement between clinical and pathological staging. To determine the prognostic value of expression of embryonic markers in tumour and nodal tissue samples. Population. Concordance study: 176 patients who underwent surgery for NSCLC with pre- and post-operative staging. Tumour study: 129 primary tumour samples from 102 patients with surgically-treated NSCLC (99% R0) and 27 lung samples. Lymph node study: 349 lymph node samples from 76 surgically-treated patients (R0: 60 pN0, 16 pN1), 27 samples from 7 pN2 patients, and 25 healthy samples. Methods. Expression of the following markers was evaluated by mRNA RT-qPCR assay: CEACAM5, FGFR2b, FRS2, MYCN, SFTPC, SHH, SHP2, and SOX17 in the tumour and lung samples and CEACAM5, FGFR2b and SHP2 in nodal tissues. Statistical analyses included kappa index, chi-squared tests, non-parametric tests, Kaplan Meier curves, log-rank and Cox regression tests, and binary or ordinal logistic regression. Results. Clinical study. Clinical and pathological staging agreed in 102 of 176 patients (58%) [kappa index, 0.54 (0.44-0.63)]. Surgical-pathological staging validated the surgical approach in 145 cases (82%); the remaining cases were classified as stage IIIA N2 (21 cases; 12%) and IIIB-IV (10 cases; 6%). Tumour study. Underexpression of SFTPC in the tumour sample was associated with a 7-fold (7.3; 1.3-40.9) greater active risk of recurrence and a nearly 5-fold (4.9; 1.04-23.2) greater risk of death. Underexpression of SHP2 was associated with a shorter disease-free survival interval (DFS) and overall survival (OS) (p=0.055). Overexpression of FGFR2b or SHH was associated with longer DFS and OS (p<0.05; for SHH, p=0.07 for OS). Combining markers did not provide any additional information. Lymph node study. The evaluation of lymph nodes based on the combined data for CEACAM5, FGFR2b and SHP2 resulted in re-classification of 219 out of 349 (63%) nodes; 68 patients (89%) were restaged as molecular-positive, as follows: 53 pN0 (88%) and 15 pN1 (94%). The course of disease was slightly worse in these molecular-positive patients (DFS/OS, p>0.05). Conclusions. Concordance between clinical and surgical-pathological staging is moderate, without affecting the surgical indication in most cases. Underexpression of SFTPC in tumour samples was independently associated with worse prognosis. Molecular restaging based on expression of CEACAM5, FGFR2b and SHP2 in lymph node tissues did not provide any additional relevant clinical information.