PMID- 19738126
OWN - NLM
STAT- MEDLINE
DCOM- 20091130
LR  - 20220321
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 27
IP  - 30
DP  - 2009 Oct 20
TI  - Amphiregulin and epiregulin mRNA expression in primary tumors predicts outcome in 
      metastatic colorectal cancer treated with cetuximab.
PG  - 5068-74
LID - 10.1200/JCO.2008.21.3744 [doi]
AB  - PURPOSE: To study the power of the epidermal growth factor receptor (EGFR) 
      epiregulin (EREG) and amphiregulin (AREG) ligands' expression in primary tumors 
      to predict the outcome in patients with chemorefractory metastatic colorectal 
      cancer (cmCRC) treated with the combination of cetuximab and irinotecan. PATIENTS 
      AND METHODS: Gene expression measurements and KRAS mutation analysis were 
      performed on archival formalin-fixed paraffin-embedded primary tumors of 220 
      cmCRC patients. Response was measured using RECIST (Response Evaluation Criteria 
      in Solid Tumors) criteria. The relation between ligand expression levels and 
      outcome was evaluated using logistic regression for response and Cox regression 
      for survival data. Receiver operating characteristics analysis was performed for 
      response and survival data. CIs for the performance indices were obtained with a 
      nonparametric bootstrap procedure. Findings were externally validated on a series 
      of 67 samples treated in a similar setting. RESULTS: In KRAS wild type (WT) 
      patients, there was a significant association between log-transformed ligand 
      expression and response for EREG (odds ratio for objective response, 1.90; 95% 
      CI, 1.27 to 2.83; P = .0005; concordance index [c-index], 0.681) and for AREG 
      (odds ratio for objective response, 1.862; 95% CI, 1.22 to 2.72; P = .0017; 
      c-index, 0.673). In a Cox regression model, dichotomized ligand expression was 
      significantly associated with progression-free survival (PFS) and overall 
      survival (OS). EREG PFS hazard ratio (HR) was 0.41 (95% CI, 0.274 to 0.609; P < 
      .001; time-dependent c-index [Ctau index], 0.640), and AREG PFS HR was 0.43 (95% 
      CI, 0.29 to 0.64; P < .001; Ctau index, 0.627). EREG OS HR was 0.42 (95% CI, 0.28 
      to 0.63; P < .0001; Ctau index, 0.639), and AREG OS HR was 0.40 (95% CI, 0.27 to 
      0.64; P < .0001; Ctau index, 0.625). There was no predictive power of ligand 
      expression in patients with KRAS mutation. CONCLUSION: Expression of EGFR ligands 
      in primary tumors significantly predicts outcome in KRAS WT cmCRC treated with 
      cetuximab and irinotecan.
FAU - Jacobs, Bart
AU  - Jacobs B
AD  - Department of Pathology, Digestive Oncology Unit, University Hospital 
      Gasthuisberg, Katholieke Universiteit Leuven, Leuven, Belgium.
FAU - De Roock, Wendy
AU  - De Roock W
FAU - Piessevaux, Hubert
AU  - Piessevaux H
FAU - Van Oirbeek, Robin
AU  - Van Oirbeek R
FAU - Biesmans, Bart
AU  - Biesmans B
FAU - De Schutter, Jef
AU  - De Schutter J
FAU - Fieuws, Steffen
AU  - Fieuws S
FAU - Vandesompele, Jo
AU  - Vandesompele J
FAU - Peeters, Marc
AU  - Peeters M
FAU - Van Laethem, Jean-Luc
AU  - Van Laethem JL
FAU - Humblet, Yves
AU  - Humblet Y
FAU - Penault-Llorca, Frederique
AU  - Penault-Llorca F
FAU - De Hertogh, Gert
AU  - De Hertogh G
FAU - Laurent-Puig, Pierre
AU  - Laurent-Puig P
FAU - Van Cutsem, Eric
AU  - Van Cutsem E
FAU - Tejpar, Sabine
AU  - Tejpar S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090908
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (AREG protein, human)
RN  - 0 (Amphiregulin)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (EGF Family of Proteins)
RN  - 0 (EREG protein, human)
RN  - 0 (Epiregulin)
RN  - 0 (Glycoproteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (KRAS protein, human)
RN  - 0 (Ligands)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Messenger)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - 7673326042 (Irinotecan)
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)
RN  - XT3Z54Z28A (Camptothecin)
SB  - IM
CIN - J Clin Oncol. 2010 Apr 10;28(11):e173-4; author reply e175-6. PMID: 20177018
MH  - Amphiregulin
MH  - Antibodies, Monoclonal/*therapeutic use
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Agents/*therapeutic use
MH  - Camptothecin/analogs & derivatives/therapeutic use
MH  - Cetuximab
MH  - Cohort Studies
MH  - Colorectal Neoplasms/drug therapy/*genetics/mortality/secondary
MH  - EGF Family of Proteins
MH  - Epidermal Growth Factor/*genetics
MH  - Epiregulin
MH  - ErbB Receptors/antagonists & inhibitors/genetics
MH  - Gene Expression
MH  - Glycoproteins/*biosynthesis/*genetics
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/*biosynthesis/*genetics
MH  - Irinotecan
MH  - Ligands
MH  - Prognosis
MH  - Proto-Oncogene Proteins/genetics
MH  - Proto-Oncogene Proteins p21(ras)
MH  - RNA, Messenger/genetics
MH  - Survival Analysis
MH  - ras Proteins/genetics
EDAT- 2009/09/10 06:00
MHDA- 2009/12/16 06:00
CRDT- 2009/09/10 06:00
PHST- 2009/09/10 06:00 [entrez]
PHST- 2009/09/10 06:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
AID - JCO.2008.21.3744 [pii]
AID - 10.1200/JCO.2008.21.3744 [doi]
PST - ppublish
SO  - J Clin Oncol. 2009 Oct 20;27(30):5068-74. doi: 10.1200/JCO.2008.21.3744. Epub 
      2009 Sep 8.