Article

Use of ERCC1 expression levels in circulating tumor cells to predict response to platinum-based chemotherapy in patients with non-small cell lung cancer

Authors:
  • KMG Klinik Silbermühle GmbH
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Abstract

7512 Background: ERCC-1 is a nucleotide excision repair gene associated with DNA repair of DNA adducts induced by platinum based chemotherapy. ERCC-1 mRNA levels have been shown to predict response in patients with NSCLC when treated with platinum based chemotherapy. We therefore examined whether ERCC1 expression levels in specifically enriched circulating tumor cells (CTC) are associated with response to platinum-based systemic first-line chemotherapy. Methods: Blood was drawn from 75 patients, treated consecutively in our institution, 1 hour before chemotherapy on days 1 and 22 of first-line chemotherapy. RECIST criteria were applied to evaluate clinical response (CT-scan). Mononuclear Cells and CTC were enriched from peripheral venous blood using a specifically designed buoyant density gradient centrifugation. After using immuno-magnetic beads with anti-CD15 and anti-CD45 monoclonal antibodies to negatively select hematopoietic cells, epithelial tumor cells were directly enriched from the residual cell suspension using magnetic beads coated with the monoclonal antibody BerEP4 against the human epithelial antigen, EpCAM. ERCC1 mRNA expression was measured using a quantitative real-time RT-PCR method. Results: ERCC1 expression levels in CTC were significantly correlated with response (p = 0.003) to platinum-based chemotherapy. Receiver Operating Characteristic (ROC) Curve Analysis was used to assess the sensitivity and the specificity of high ERCC1 expression (> 75th percentile) to distinguish disease control (response or stable disease) from progressive disease. The sensitivity (true positive rate) was 75% and the specificity (true negative rate) 81.3%. The area under the curve was 0.78 (CI 0.612 to 0.901) with a significance level of p = 0.04. Conclusions: These results suggest that ERCC1 gene expression levels in circulating tumor cells in patients with non-small cell lung cancer predict response prior to first-line chemotherapy. ERCC1 gene expression levels may therefore allow the selection of patients who benefit likely from platinum-based chemotherapy. Further studies are warranted to study this association. No significant financial relationships to disclose.

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... 27 Nevertheless, these studies were done in biopsy specimens and, in most instances, required a second biopsy to obtain sufficient tissue to perform the ERCC1 analysis. Hoffmann et al., 28 in an effort to eliminate the need for a second biopsy, examined whether ERCC1 expression levels in specifically enriched circulating tumor cells (CTCs) were associated with response to platinum-based chemotherapy. Blood was drawn from 75 consecutively treated patients with advanced NSCLC 1 hour before chemotherapy on days 1 and 22 of first-line chemotherapy. ...
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