Epidermal growth factor receptor gene copy number in 101 advanced colorectal cancer patients treated with chemotherapy plus cetuximab

Journal of Translational Medicine

Research

Roberta Merola¹  Anna Cianciulli¹  Carla Campanella²  Giancarlo Paoletti²  Angela Torsello²  Carlo Garufi²  Francesco Cognetti²  Massimo Zeuli²  Marcella Mottolese³  Maria Grazia Diodoro³  Elisa Melucci³  Salvatore Conti³  Isabella Sperduti⁴ 

[1] Department of Clinical Pathology, Regina Elena Institute, via E Chianesi 53, 00144, Rome, Italy;Department of Medical Oncology, Regina Elena Institute, via E Chianesi 53, 00144, Rome, Italy;Department of Pathology, Regina Elena Institute, via E Chianesi 53, 00144, Rome, Italy;Department of Statistics, Regina Elena Institute, via E Chianesi 53, 00144, Rome, Italy;

关键词: Overall Survival;    Epidermal Growth Factor Receptor;    Cetuximab;    Gene Copy Number;    Epidermal Growth Factor Receptor Expression;   

DOI  :  10.1186/1479-5876-8-36

 received in 2009-06-12, accepted in 2010-04-16,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundResponsiveness to Cetuximab alone can be mediated by an increase of Epidermal Growth factor Receptor (EGFR) Gene Copy Number (GCN). Aim of this study was to assess the role of EGFR-GCN in advanced colorectal cancer (CRC) patients receiving chemotherapy plus Cetuximab.MethodsOne hundred and one advanced CRC patients (43 untreated- and 58 pre-treated) were retrospectively studied by fluorescence in situ hybridization (FISH) to assess EGFR-GCN and by immunohistochemistry (IHC) to determine EGFR expression. Sixty-one out of 101 patients were evaluated also for k-ras status by direct sequencing. Clinical end-points were response rate (RR), progression-free survival (PFS) and overall survival (OS).ResultsIncreased EGFR-GCN was found in 60/101 (59%) tumor samples. There was no correlation between intensity of EGFR-IHC and EGFR-GCN (p = 0.43). Patients receiving chemotherapy plus Cetuximab as first line treatment had a RR of 70% (30/43) while it was 18% (10/56) in the group with previous lines of therapy (p < 0.0001). RR was observed in 29/60 (48%) of patients with increased EGFR-GCN and in 6/28 (21%) in those without (p = 0.02). At multivariate analyses, number of chemotherapy lines and increased EGFR-GCN were predictive of response; EGFR-IHC score, increased EGFR-GCN and number of chemotherapy lines were significantly associated with a significant better PFS. Response to therapy was the only prognostic predictive factor for OS. In the 60 patients analyzed for k-ras mutations, number of chemotherapy lines, increased EGFR-GCN and k-ras wild type status predicted a better PFS.ConclusionIn metastatic CRC patients treated with chemotherapy plus Cetuximab number of chemotherapy lines and increased EGFR-GCN were significantly associated with a better clinical outcome, independent of k-ras status.

【 授权许可】

Unknown   
© Campanella et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.