The Prognostic Significance of Multiple Molecular Markers in Blood of Patients With Multimodal Treatment of Esophageal Cancer
Jan Brabender*, Peter P. Grimminger, Arnulf H. HöLscher, Daniel Vallbohmer, Elfriede Bollschweiler, Ralf Metzger
Department of Surgery, University of Cologne, Cologne, Germany
Background: Aim of this study was to evaluate the prognostic significance of ERCC1 (Excision Repair Cross Complementing gene), COX2 (cyclooxygenase-2), TS (thymidylate synthase), DPD (Dihydropyrimidine-Dehydrogenase)-RNA expression and the single-nucleotide-polymorphisms (SNP) of ERCC1, GNAS, and XRCC1 in blood of patients with neoadjuvant treated cancer of the esophagus. Material and methods: A total of 29 patients with locally advanced cancer (cT3-T4, Nx, M0) of the esophagus were included in this study. Blood samples from each patient were drawn prior to neoadjuvant radio-chemotherapy (cis-Platin, 5-FU, 36Gy). Transthoracic en-bloc esophagectomy was performed in all patients following completion of neadjuvant therapy. After extraction of cellular tumor-RNA from sera samples, quantitative molecular analysis was done by real-time RT-PCR (Taqman©). Histomorphological regression was defined as major response when resected specimen contained <10% of residual vital tumor cells, and minor response with >10% of vital residual tumor cells. Results: Nineteen of 29 (65.5%) of patients showed a minor histopathological response and 10 of 29 (34.5%) showed a major-response to neadjuvant radio-chemotherapy. The median survival of patients was 2.08 years (0.15-4.53). Blood TS RNA expression and the ERCC1 C118T SNP were significantly associated with patient’s survival. Patients with a high TS expression had a median survival of 1.1 years (0.21-3.16) compared to 3.36 years for patient’s with a low TS expression (p=0.031, Logrank test). Patient’s with the ERCC1 genotype GG had a median survival of 0.3 years (0.1-0.5) compared to 2.8 years (0.4-1.9) for the AG genotype and 3.0 years (0.4-2.2) for the AA genotype (p<0.001). There were no associations between patient’s clinical variables and gene expression status.Conclusions: TS RNA expression and the ERCC1 C118T SNP in blood are associated with the prognosis of patients with neoadjuvant treated esophageal cancer and are potential non-invasive prognostic markers in this disease. Future studies are warranted to determine the clinical potential of this molecular approach.
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