Potential der ERCC1 und c-erbB-2 Genexpression zur Prädiktion des Responseverhaltens auf die neoadjuvante Radiochemotherapie beim Ösophaguscarcinom
Objective: ERCC1 encodes for a nucleotide excision repair (NER) gene involved in repair of radiation and chemotherapy induced DNA-damage, especially cis-platinum (CDDP) mediated interstrand crosslinks. The c-erbB-2 gene also known as HER2/neu is coding for a transmembrane glycoprotein (pl85) with tyrosine kinase activity being a member of the type 1 growth factor receptor family. We examined the potential of ERCC1 as well as c-erbB-2 mRNA expression to predict response and non-response in patients with locally advanced esophageal cancer treated with neoadjuvant radiochemotherapy. Methods: 30 patients with resectable, locally advanced esophageal cancer (cT3,Nx,M0) underwent neoadjuvant radiochemotherapy (CDDP, 5-FU, 36Gy). All tumors were resected by transthoracic en bloc esophagectomy and objective histomorphologic regression was defined: Grade I: minor response/no change (< 50% regression), II: partial response with 10 – 50% residual vital tumor cells, III: near complete response with < 10% residual vital tumor cells, and grade IV with histomorphologic complete remission (pCR, ypT0). Objective histomorphologic regression was defined as major response when < 10% residual vital tumor cells or pathologic complete response (pCR) was accomplished (Grade III, IV).
Tissue samples were collected by endoscopic biopsy prior to treatment. Quantitation of ERCC1 and c-erbB-2 mRNA expression was performed using quantitative real time RTPCR with specific primers using β-actin as internal control. Relative ERCC1 or c-erbB-2 expression was calculated as (ERCC1 or c-erbB-2/β-actin in tumor)/(ERCCl or c-erbB-2/β-actin in paired normal tissue). Results: Comparison of quantitative gene expression to histomorphologic regression showed that relative ERCC1 and/or c-erbB-2 expression levels > 1.12 were not associated with major response (grade III, IV) to radiochemotherapy. With this approach 12/30 patients were identified having no major response after neoadjuvant radiochemotherapy. Conclusion: Our study shows that quantitative ERCC1 and c-erbB-2 mRNA expression could serve as a predictor of response identifying those patients with esophageal cancer who will not benefit from neoadjuvant radiochemotherapy.
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