PMID- 20884623
OWN - NLM
STAT- MEDLINE
DCOM- 20110628
LR  - 20181201
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Linking)
VI  - 17
IP  - 2
DP  - 2011 Jan 15
TI  - EGFR fluorescence in situ hybridization pattern of chromosome 7 disomy predicts 
      resistance to cetuximab in KRAS wild-type metastatic colorectal cancer patients.
PG  - 382-90
LID - 10.1158/1078-0432.CCR-10-0208 [doi]
AB  - PURPOSE: Metastatic colorectal cancer patients with low epidermal growth factor 
      receptor (EGFR) gene copy number are unlikely to respond to anti-EGFR monoclonal 
      antibody (mAb) treatment. The objective of this study was to investigate EGFR 
      fluorescence in situ hybridization (FISH) patterns of chromosome 7 disomy with 
      efficacy of cetuximab therapy in metastatic colorectal cancer patients. 
      EXPERIMENTAL DESIGN: We detected the EGFR FISH patterns and KRAS status in 74 
      tumors from cetuximab-treated metastatic colorectal cancer patients and analyzed 
      with response rate (RR) and progression-free survival (PFS). RESULTS: One of the 
      16 (6.25%) patients with chromosome 7 homogeneous disomy (defined as FISH 
      negative) had objective response to cetuximab. A total of 53(76.8%) patients with 
      chromosome 7 pattern of variable ratios of disomy versus polysomy (defined as 
      FISH positive) had a significantly higher RR (37.7% versus 6.25%; P = 0.01), a 
      trend towards longer PFS (4.5 versus 2.9 months; P = 0.07). Among 54 KRAS 
      wild-type patients, EGFR FISH-positive patients had significantly higher RR 
      (51.3% versus 9%; P = 0.01) and longer PFS (5.0 versus 2.3 months; P = 0.02) than 
      EGFR FISH-negative patients. However, among 20 KRAS mutant-type patients, there 
      was no difference in RR (0% versus 0%) and PFS (2.5 versus 3.8 months; P = 0.51) 
      between EGFR FISH-positive and -negative patients. CONCLUSION: Our results show 
      firstly that patients with EGFR FISH pattern of chromosome 7 disomy have a very 
      low chance to benefit from cetuximab-based therapy. EGFR FISH pattern of 
      chromosome 7 disomy may be as a negative predicative factor for cetuximab 
      response in KRAS wild-type metastatic colorectal cancer patients.
CI  - (c)2011 AACR.
FAU - Li, Yu-Hong
AU  - Li YH
AD  - State Key Laboratory of Oncology in Southern China, Guangzhou, People's Republic 
      of China.
FAU - Wang, Fang
AU  - Wang F
FAU - Shen, Lin
AU  - Shen L
FAU - Deng, Yan-Ming
AU  - Deng YM
FAU - Shao, Qiong
AU  - Shao Q
FAU - Feng, Fen
AU  - Feng F
FAU - An, Xin
AU  - An X
FAU - Wang, Feng-Hua
AU  - Wang FH
FAU - Wang, Zhi-Qiang
AU  - Wang ZQ
FAU - Xu, Rui-Hua
AU  - Xu RH
FAU - Shao, Jian-Yong
AU  - Shao JY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100930
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - EC 2.7.10.1 (ErbB Receptors)
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  - *Chromosomes, Human, Pair 7
MH  - Colorectal Neoplasms/drug therapy/*genetics
MH  - Disease-Free Survival
MH  - ErbB Receptors/immunology
MH  - Female
MH  - Gene Dosage
MH  - *Genes, erbB-1
MH  - Genes, ras
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Retrospective Studies
MH  - Uniparental Disomy
EDAT- 2010/10/05 06:00
MHDA- 2011/06/29 06:00
CRDT- 2010/10/02 06:00
PHST- 2010/10/02 06:00 [entrez]
PHST- 2010/10/05 06:00 [pubmed]
PHST- 2011/06/29 06:00 [medline]
AID - 1078-0432.CCR-10-0208 [pii]
AID - 10.1158/1078-0432.CCR-10-0208 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2011 Jan 15;17(2):382-90. doi: 10.1158/1078-0432.CCR-10-0208. 
      Epub 2010 Sep 30.