PMID- 10632352
OWN - NLM
STAT- MEDLINE
DCOM- 20000214
LR  - 20071114
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 5
IP  - 12
DP  - 1999 Dec
TI  - Genetic alterations in ERBB2-amplified breast carcinomas.
PG  - 4140-5
AB  - Amplification of the ERBB2 oncogene has recently received attention as a target 
      for antibody-based therapies and as a predictor of response to adjuvant 
      chemotherapy. Modification of treatment strategies based on ERBB2 status has led 
      to further interest in the genetic alterations that accompany ERBB2 gene 
      amplification or overexpression. In this study, chromosome alterations that are 
      associated with ERBB2 amplification were defined by comparative genomic 
      hybridization (CGH). Additionally, fluorescence in situ hybridization (FISH) was 
      used to validate gene amplification, and protein expression was detected 
      immunohistochemically. ERBB2-amplified tumors as detected by FISH, 
      immunohistochemistry (IHC), or CGH had twice as many CGH-defined chromosomal 
      alterations (means of 11.8, 11.0, and 12.7, respectively) as the nonamplified 
      tumors (means of 6.8, 7.0, and 5.6, respectively). ERBB2 positivity correlated 
      with the total number of genetic events. A wide spectrum of copy number gains and 
      losses was seen by CGH in all of the tumors. An increased number of losses of 18q 
      and gains of 20q was found in ERBB2-positive tumors. Other common aberrations for 
      all of the tumors were copy number gains of 1q (58%), 8q (52%), 20q (30%), and 
      losses of 18q (39%), 13q (39%), and 3p (33%). A high degree of concordance was 
      observed among the three methods in 33 primary breast cancers. The concurrence 
      for ERBB2 detection between FISH and IHC was 90%, between FISH and CGH was 82%, 
      and between IHC and CGH was 84%. This study shows that breast tumors showing 
      erbB2 overexpression or gene amplification are genetically distinct from 
      erbB2-negative tumors. These differences may relate to the mechanisms underlying 
      altered response to adjuvant therapies and may define the responsiveness to 
      erbB2-directed immunotherapy.
FAU - Isola, J
AU  - Isola J
AD  - Laboratory of Cancer Genetics, University and University Hospital of Tampere, 
      Finland.
FAU - Chu, L
AU  - Chu L
FAU - DeVries, S
AU  - DeVries S
FAU - Matsumura, K
AU  - Matsumura K
FAU - Chew, K
AU  - Chew K
FAU - Ljung, B M
AU  - Ljung BM
FAU - Waldman, F M
AU  - Waldman FM
LA  - eng
GR  - CA 44768/CA/NCI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
SB  - IM
MH  - Breast Neoplasms/*genetics/metabolism/pathology
MH  - Female
MH  - *Gene Amplification
MH  - Genes, erbB-2/*genetics
MH  - Humans
MH  - In Situ Hybridization
MH  - In Situ Hybridization, Fluorescence
MH  - Middle Aged
MH  - Nucleic Acid Hybridization
MH  - Tumor Cells, Cultured
EDAT- 2000/01/13 09:00
MHDA- 2000/02/19 09:00
CRDT- 2000/01/13 09:00
PHST- 2000/01/13 09:00 [pubmed]
PHST- 2000/02/19 09:00 [medline]
PHST- 2000/01/13 09:00 [entrez]
PST - ppublish
SO  - Clin Cancer Res. 1999 Dec;5(12):4140-5.