Excision Repair Cross Complementing (ERCC1) Gen-Expression als prädiktiver Response-Parameter der neoadjuvanten Radiochemotherapie beim Ösophaguscarcinom

Abstract

Objective: ERCC1 encodes for an excision repair gene involved in repair of radiation and cis-platinum induced DNA-damage. We examined the potential of ERCC1 mRNA expression to predict response in patients with esophageal cancer treated with neoadjuvant radiochemotherapy. Methods: Twenty-four patients with resectable, locally advanced esophageal cancer (cT3,Nx,36 Gy) underwent neoadjuvant radiochemotherapy (CDDP, 5-FU, 36 Gy). All tumors were resected by transthoracic en bloc esophagectomy and objective histomorphologic regression was defined as major response when less than 10% of residual vital tumor cells or pathologic complete response (pCR) was accomplished. Tissue samples were collected by endoscopic biopsy prior to treatment. Quantitation of ERCC1 mRNA expression was performed using quantitative real time RT-PCR with specific primers using β-actin as internal control. Relative ERCC1 expression was calculated as: (ERCC1/β-actin in tumor)/(ERCC1/β-actin in paired normal tissue). Results Median relative ERCC1 mRNA expression was 0.83. Comparison of ERCC1 gene expression to histomorphologic regression showed that relative expression levels of more than 1.12 were not associated with major response to radiochemotherapy. Conclusion: Our study shows that quantitative ERCC1 mRNA expression could serve as a predictor of response, identifying patients with esophageal cancer who will not benefit from neoadjuvant radiochemotherapy.