Georgios Tsakonas1, Johan Botling2, Patrick Micke2, Chris Rivard3, Linnea LaFleur2, Johanna Mattsson2, Teresa Boyle3, Fred R Hirsch3, Simon Ekman4. 1. Thoracic Oncology Center, Theme Cancer, Karolinska University Hospital/Department of Oncology- Pathology, Karolinska Institutet, Stockholm, Sweden. Electronic address: georgios.tsakonas@ki.se. 2. Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden. 3. Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. 4. Thoracic Oncology Center, Theme Cancer, Karolinska University Hospital/Department of Oncology- Pathology, Karolinska Institutet, Stockholm, Sweden.
Abstract
BACKGROUND: c-MET protein overexpression has been proposed as a biomarker in non-small cell lung cancer (NSCLC), albeit its role in the clinical setting has not been firmly established yet. PATIENTS AND METHODS: We designed a retrospective cohort study, consisting of 725 patients with surgically removed NSCLC. Immunohistochemistry (IHC) was conducted in tissue microarrays (TMA) from lung tumors and healthy tissue. IHC staining was quantified using H-scores (range 0-300). Association between c-MET H-score and overall survival (OS) as well as progression-free survival (PFS) was explored. RESULTS: c-MET H-score ≥20 had a significant positive impact on OS in the multivariate analysis in the whole study population, HR = 0.79 (95%CI: 0.64-0.97). The prognostic effect of c-MET H-score ≥20 was even stronger in patients who received adjuvant treatment with a HR = 0.61 (95% CI: 0.40-0.93). In the subgroup of adenocarcinoma and squamous cell carcinoma patients with stage IIA-IIIB disease, the prognostic impact of c-MET was significant in the univariate analysis (HR = 0.60, 95% CI: 0.43-0.83). CONCLUSION: c-MET H-score ≥20 is a positive prognostic biomarker for OS in early stage NSCLC. This benefit seems to be strongly correlated to adjuvant chemotherapy, therefore rendering c-MET H-score ≥20 a possible predictive biomarker for platinum-based adjuvant chemotherapy in early stage NSCLC.
BACKGROUND:c-MET protein overexpression has been proposed as a biomarker in non-small cell lung cancer (NSCLC), albeit its role in the clinical setting has not been firmly established yet. PATIENTS AND METHODS: We designed a retrospective cohort study, consisting of 725 patients with surgically removed NSCLC. Immunohistochemistry (IHC) was conducted in tissue microarrays (TMA) from lung tumors and healthy tissue. IHC staining was quantified using H-scores (range 0-300). Association between c-MET H-score and overall survival (OS) as well as progression-free survival (PFS) was explored. RESULTS:c-MET H-score ≥20 had a significant positive impact on OS in the multivariate analysis in the whole study population, HR = 0.79 (95%CI: 0.64-0.97). The prognostic effect of c-MET H-score ≥20 was even stronger in patients who received adjuvant treatment with a HR = 0.61 (95% CI: 0.40-0.93). In the subgroup of adenocarcinoma and squamous cell carcinomapatients with stage IIA-IIIB disease, the prognostic impact of c-MET was significant in the univariate analysis (HR = 0.60, 95% CI: 0.43-0.83). CONCLUSION:c-MET H-score ≥20 is a positive prognostic biomarker for OS in early stage NSCLC. This benefit seems to be strongly correlated to adjuvant chemotherapy, therefore rendering c-MET H-score ≥20 a possible predictive biomarker for platinum-based adjuvant chemotherapy in early stage NSCLC.
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