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BackgroundCentral nervous system is a common site of metastasis in NSCLC and confers worse prognosis and quality of life. The aim of this prospective study was to evaluate the prognostic significance of clinical-pathological factors (CPF), serum CEA levels, and EGFR and HER2 tissue-expression in brain metastasis (BM) and overall survival (OS) in patients with advanced NSCLC.MethodsIn a prospective manner, we studied 293 patients with NSCLC in IIIB-IV clinical stage. They received standard chemotherapy. CEA was measured prior to treatment; EGFR and HER2 were evaluated by immunohistochemistry. BM development was confirmed by MRI in symptomatic patients.ResultsBM developed in 27, and 32% of patients at 1 and 2 years of diagnosis with adenocarcinoma (RR 5.2; 95% CI, 1.002–29; p = 0.05) and CEA ≥ 40 ng/mL (RR 11.4; 95% CI, 1.7–74; p < 0.01) as independent associated factors. EGFR and HER2 were not statistically significant. Masculine gender (RR 1.4; 95% CI, 1.002–1.9; p = 0.048), poor performance status (RR 1.8; 95% CI, 1.5–2.3; p = 0.002), advanced clinical stage (RR 1.44; 95% CI, 1.02–2; p = 0.04), CEA ≥ 40 ng/mL (RR 1.5; 95% CI, 1.09–2.2; p = 0.014) and EGFR expression (RR 1.6; 95% CI, 1.4–1.9; p = 0.012) were independent associated factors to worse OS.ConclusionHigh CEA serum level is a risk factor for BM development and is associated with poor prognosis in patients with advanced NSCLC. Surface expression of CEA in tumor cells could be the physiopathological mechanism for invasion to CNS.

Background: One of the risk factors associated with lung cancer in never-smoker patients is wood smoke exposure (WS). However, information about its clinical and molecular characteristics remains scant. Objective: This was to analyze - in plasma from patients with tobacco- or wood-smoke-induced lung cancer - whether the enzymatic activity and concentration of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) differ, and to determine whether there was a correlation between these indicators of the metastatic potential and the first-line chemotherapy response. Methods: Patients were classified according to lung cancer associated with: the smoking of tobacco (T), WS and where no association with a known risk factor (N) could be established. The gelatinase activity of plasma MMP was analyzed by radiolabeled substrate degradation and zymography assay. Protein expression of MMPs and TIMPs was evaluated by Western blot densitometry analysis. Results: The 26.9% WS patients had a better response to therapy in comparison with the T group (OR = 4.9, 95% CI = 1.25-20.15; p = 0.019). The lowest gelatinase activity was observed in WS subjects, in comparison with T and N subjects (96.7 ± 15.9, 182.9 ± 31.5 and 163.3 ± 22.7 µg of degraded gelatin/mg of incubated plasma protein, respectively; p < 0.025); this enzymatic activity corresponded to MMP-2. The highest MMP-2, MMP-9, MT1-MMP and TIMP-1 plasma levels were observed in T subjects. Conclusion: Tobacco and wood smoke have different effects on MMP and TIMP synthesis and gelatinase activity, directly influencing lung cancer metastatic potential and chemotherapy response.

Patients with progression of lung adenocarcinoma, mainly from the LCT group, had an increase in gelatinase activity compared with subjects that responded to chemotherapy. Therefore, plasma gelatinase activity, particularly MMP-2 enzymatic activity, could be used as a way to assess lung adenocarcinoma progression as well as an indicator for the use of MMP-2 inhibitors.

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