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

Carla Campanella, Marcella Mottolese, Anna Cianciulli, Angela Torsello, Roberta Merola, Isabella Sperduti, Elisa Melucci, Salvatore Conti, Maria G. Diodoro, Massimo Zeuli, Giancarlo Paoletti, Francesco Cognetti, Carlo Garufi

Research output: Contribution to journalArticle

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Abstract

Background: Responsiveness 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.Methods: One 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).Results: Increased 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.Conclusion: In 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.

Original languageEnglish
Article number36
JournalJournal of Translational Medicine
Volume8
DOIs
Publication statusPublished - Apr 16 2010

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erbB-1 Genes
Chemotherapy
Gene Dosage
Epidermal Growth Factor Receptor
Colorectal Neoplasms
Genes
Drug Therapy
Disease-Free Survival
Immunohistochemistry
Cetuximab
Survival
Fluorescence In Situ Hybridization
Therapeutics
Multivariate Analysis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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Epidermal growth factor receptor gene copy number in 101 advanced colorectal cancer patients treated with chemotherapy plus cetuximab. / Campanella, Carla; Mottolese, Marcella; Cianciulli, Anna; Torsello, Angela; Merola, Roberta; Sperduti, Isabella; Melucci, Elisa; Conti, Salvatore; Diodoro, Maria G.; Zeuli, Massimo; Paoletti, Giancarlo; Cognetti, Francesco; Garufi, Carlo.

In: Journal of Translational Medicine, Vol. 8, 36, 16.04.2010.

Research output: Contribution to journalArticle

Campanella, C, Mottolese, M, Cianciulli, A, Torsello, A, Merola, R, Sperduti, I, Melucci, E, Conti, S, Diodoro, MG, Zeuli, M, Paoletti, G, Cognetti, F & Garufi, C 2010, 'Epidermal growth factor receptor gene copy number in 101 advanced colorectal cancer patients treated with chemotherapy plus cetuximab', Journal of Translational Medicine, vol. 8, 36. https://doi.org/10.1186/1479-5876-8-36
Campanella, Carla ; Mottolese, Marcella ; Cianciulli, Anna ; Torsello, Angela ; Merola, Roberta ; Sperduti, Isabella ; Melucci, Elisa ; Conti, Salvatore ; Diodoro, Maria G. ; Zeuli, Massimo ; Paoletti, Giancarlo ; Cognetti, Francesco ; Garufi, Carlo. / Epidermal growth factor receptor gene copy number in 101 advanced colorectal cancer patients treated with chemotherapy plus cetuximab. In: Journal of Translational Medicine. 2010 ; Vol. 8.
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abstract = "Background: Responsiveness 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.Methods: One 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).Results: Increased 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.Conclusion: In 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.",
author = "Carla Campanella and Marcella Mottolese and Anna Cianciulli and Angela Torsello and Roberta Merola and Isabella Sperduti and Elisa Melucci and Salvatore Conti and Diodoro, {Maria G.} and Massimo Zeuli and Giancarlo Paoletti and Francesco Cognetti and Carlo Garufi",
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T1 - Epidermal growth factor receptor gene copy number in 101 advanced colorectal cancer patients treated with chemotherapy plus cetuximab

AU - Campanella, Carla

AU - Mottolese, Marcella

AU - Cianciulli, Anna

AU - Torsello, Angela

AU - Merola, Roberta

AU - Sperduti, Isabella

AU - Melucci, Elisa

AU - Conti, Salvatore

AU - Diodoro, Maria G.

AU - Zeuli, Massimo

AU - Paoletti, Giancarlo

AU - Cognetti, Francesco

AU - Garufi, Carlo

PY - 2010/4/16

Y1 - 2010/4/16

N2 - Background: Responsiveness 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.Methods: One 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).Results: Increased 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.Conclusion: In 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.

AB - Background: Responsiveness 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.Methods: One 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).Results: Increased 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.Conclusion: In 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.

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