Neoadjuvant Radiochemotherapy in Adenocarcinoma of the Esophagus: ERCC1 Gene Polymorphisms for Prediction of Response and Prognosis

• Published in: Journal of gastrointestinal surgery 2012, Vol.16 (1), p.26-34
• Main Authors: Metzger, Ralf, Warnecke-Eberz, Ute, Alakus, Hakan, Kütting, Fabian, Brabender, Jan, Vallböhmer, Daniel, Grimminger, Peter P., Mönig, Stefan P., Drebber, Uta, Hölscher, Arnulf H., Bollschweiler, Elfriede
• Format: Article
• Language: English
• Subjects: 2011 SSAT Plenary Presentation; Adenocarcinoma - genetics; Adenocarcinoma - pathology; Adenocarcinoma - therapy; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cancer surgery; Cancer therapies; Chemoradiotherapy; Chemotherapy; Cisplatin - administration & dosage; DNA damage; DNA-Binding Proteins - genetics; Dose Fractionation, Radiation; Endonucleases - genetics; Esophageal cancer; Esophageal Neoplasms - genetics; Esophageal Neoplasms - pathology; Esophageal Neoplasms - therapy; Fluorouracil - administration & dosage; Gastroenterology; Genotype; Humans; Kaplan-Meier Estimate; Male; Medical prognosis; Medicine; Medicine & Public Health; Middle Aged; Neoadjuvant Therapy; Polymorphism; Polymorphism, Single Nucleotide; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Radiation therapy; Remission Induction; Statistics, Nonparametric; Surgery; Young Adult
• ISSN: 1091-255X; 1873-4626
• DOI: 10.1007/s11605-011-1700-x

Introduction Neoadjuvant radiochemotherapy (RT/CTx) regimens were primarily designed for treatment of squamous cell carcinoma of the esophagus. Own preliminary results demonstrate that also patients with locally advanced adenocarcinoma of the esophagus may achieve a major response in 30% with a 3-year survival rate of 80%. To identify these patients, ERCC1 (rs11615) gene polymorphisms were analyzed. ERCC1 is a key enzyme of the nucleotide excision and repair (NER) complex to prevent DNA inter- and intra-strand crosslinks. Patients and Methods Genomic DNA from 217 patients with cT3/4 adenocarcinoma of the esophagus was extracted from paraffin-embedded tissues. Of these patients, 153 underwent neoadjuvant RT/CTx (CDDP, 5-FU, 36 Gy). For analysis of ERCC1 single nucleotide polymorphisms (SNPs), allelic discrimination was performed by quantitative real-time PCR. Two allele-specific TaqMan probes in competition were used for amplification of ERCC1 (rs11615). Allelic genotyping was correlated with histomorphologic tumor regression after neoadjuvant RT/CTx and survival. Major response (MaHR) was defined as