PMID- 20398370
OWN - NLM
STAT- MEDLINE
DCOM- 20100803
LR  - 20211020
IS  - 1479-5876 (Electronic)
IS  - 1479-5876 (Linking)
VI  - 8
DP  - 2010 Apr 16
TI  - Epidermal growth factor receptor gene copy number in 101 advanced colorectal 
      cancer patients treated with chemotherapy plus cetuximab.
PG  - 36
LID - 10.1186/1479-5876-8-36 [doi]
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.
FAU - Campanella, Carla
AU  - Campanella C
AD  - Department of Medical Oncology, Regina Elena Institute, Rome, Italy.
FAU - Mottolese, Marcella
AU  - Mottolese M
FAU - Cianciulli, Anna
AU  - Cianciulli A
FAU - Torsello, Angela
AU  - Torsello A
FAU - Merola, Roberta
AU  - Merola R
FAU - Sperduti, Isabella
AU  - Sperduti I
FAU - Melucci, Elisa
AU  - Melucci E
FAU - Conti, Salvatore
AU  - Conti S
FAU - Diodoro, Maria Grazia
AU  - Diodoro MG
FAU - Zeuli, Massimo
AU  - Zeuli M
FAU - Paoletti, Giancarlo
AU  - Paoletti G
FAU - Cognetti, Francesco
AU  - Cognetti F
FAU - Garufi, Carlo
AU  - Garufi C
LA  - eng
PT  - Journal Article
DEP - 20100416
PL  - England
TA  - J Transl Med
JT  - Journal of translational medicine
JID - 101190741
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (KRAS protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
RN  - EC 3.6.5.2 (ras Proteins)
RN  - PQX0D8J21J (Cetuximab)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Monoclonal/*therapeutic use
MH  - Antibodies, Monoclonal, Humanized
MH  - Cetuximab
MH  - Colorectal Neoplasms/*drug therapy/*genetics/pathology
MH  - Disease-Free Survival
MH  - ErbB Receptors/*genetics
MH  - Female
MH  - Gene Dosage/*genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Middle Aged
MH  - Multivariate Analysis
MH  - Neoplasm Staging
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins p21(ras)
MH  - Treatment Outcome
MH  - ras Proteins/metabolism
PMC - PMC2867799
EDAT- 2010/04/20 06:00
MHDA- 2010/08/04 06:00
PMCR- 2010/04/16
CRDT- 2010/04/20 06:00
PHST- 2009/06/12 00:00 [received]
PHST- 2010/04/16 00:00 [accepted]
PHST- 2010/04/20 06:00 [entrez]
PHST- 2010/04/20 06:00 [pubmed]
PHST- 2010/08/04 06:00 [medline]
PHST- 2010/04/16 00:00 [pmc-release]
AID - 1479-5876-8-36 [pii]
AID - 10.1186/1479-5876-8-36 [doi]
PST - epublish
SO  - J Transl Med. 2010 Apr 16;8:36. doi: 10.1186/1479-5876-8-36.