engleski

Biomarkers EGFR, ERCC1, RRM1, CYFRA21-1, NSE, ProGRP And CEA In The Diagnosis, Therapy Selection And Follow-Up Of NSCLC

RATIONALE: Lung cancer is the biggest epidemiological problem. The aim of this study was through personalized approach of the clinical application biomarkers in surgicaly treated NSCLC patients improve diagnosis, selection of additional therapy and its monitoring. METHODS: From 2007 to 2009 75 NSCLC patients, stage IA - IIIA were surgicaly treated. Biomarkers CYFRA 21-1, CEA in plasma and NSE, ProGRP in serum were measured in all patients at the time of diagnosis. Molecular biomarkers EGFR, ERCC1 and RRM1 were measured from tissue samples taken during surgery in all NSCLC. The level of expression ERCC1, RRM1 and EGFR genes were determined by relative expression method. Mutation analysis of EGFR was also done. Patients were follow –up at usual control appointments with standard clinical methods and biomarkers CYFRA 21-1, NSE, CEA and ProGRP according to the pathohistological type. 47 patients were treated with standard chemotherapy protocols and/or irradiation and EGFR- thyrosine kinase inhibitors. RESULTS: Sensitivity CYFRA 21-1, NSE, CEA, ProGRP in NSCLC at the time of diagnosis was 79%, 30%, 29%, 45% (specificity of 95%). At the same time level of relative expression ERCC1, RRM1 and EGFR genes ranged from 0.01 – 65. EGFR gene mutation was in 8% patients. There was significant correlation between level of CYFRA 21-1, CEA and EGFR mutations in NSCLC at the time of diagnosis (p <0.001, p <0.004). From the 47 patients with additional therapy, 40% had a partial response to therapy. In 15% patients was progression of the disease and tumor histology replased with another type (adenocarcinoma with squamous cell carcinoma, squamous cell carcinoma with large cell carcinoma or adenocarcinoma) or adenocarcinoma with disease progression and biological activity of the tumor according to longitudinally measured biomarkers CYFRA 21-1 and CEA. Of the remaining 45% with good response to therapy were adenocarcinoma which didn’t live longer than 3 years as opposed to 20% squamous cell carcinoma. CONCLUSIONS: At the time of diagnosis CYFRA 21-1 and CEA were the most sensitive biomarkers for NSCLC without neuroendocrine components. Determination of EGFR mutations and longitudinal follow-up the CYFRA 21-1 are prognostic factor in NSCLC, especially in adenocarcinoma who recived treatment of EGFR tyrsine kinase inhibitor.

Lung cancer; biomarkers

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