PMID- 11906444
OWN - NLM
STAT- MEDLINE
DCOM- 20020418
LR  - 20191210
IS  - 1075-122X (Print)
IS  - 1075-122X (Linking)
VI  - 7
IP  - 5
DP  - 2001 Sep-Oct
TI  - Her-2/neu gene amplification in low to moderately expressing breast cancers: 
      possible role of chromosome 17/Her-2/neu polysomy.
PG  - 337-44
AB  - Overexpression of the Her-2/neu (HER2) oncogene is known to confer important 
      prognostic and predictive value to patients with breast cancer. Controversy 
      exists as to the best method for its determination caused primarily by the 
      variable sensitivities of the different antibodies and interobserver differences, 
      particularly in the group of breast cancers with borderline levels of expression 
      of the protein product. This study was therefore designed to determine the status 
      of the HER2 gene amplification in a group of breast carcinomas with low levels of 
      overexpression. After an initial validation of our procedures, a series of 52 
      consecutive cases of formalin-fixed, paraffin-embedded breast cancers with low 
      levels of overexpression and a series of 22 cases with no expression by 
      immunohistochemistry were analyzed by fluorescence in situ hybridization (FISH), 
      and the results correlated statistically. Amplification of the HER2 gene was 
      observed in 16% of equivocal to weakly positive cases. Those that were amplified 
      showed low levels of amplification with ratios less than 4.5 and a characteristic 
      scattered pattern of distribution of HER2 signals in the FISH assay. In addition, 
      heterogeneity was noted in two cases in the amplification of the HER2 gene within 
      the same tumor samples with pockets of amplified tumor cells amidst nonamplified 
      tumor cells. In cases without amplification, a statistically significant number 
      showed chromosome 17 polysomy. In conclusion, equivocal to low levels of HER2 
      overexpression in breast cancers are associated, in the majority of cases, with 
      chromosome 17 polysomy and a corresponding increase in the HER2 gene numbers. 
      True gene amplification is present in only a minority of cases. FISH analysis 
      should be used for confirmation of gene amplification. Prior screening and 
      selection of appropriate immunohistochemistry-positive areas for FISH analysis 
      may prove beneficial.
FAU - Bose, S
AU  - Bose S
AD  - UCLA School of Medicine, Department of Pathology and Lab Medicine, Los Angeles, 
      CA 90095-1763, USA. sbose@mednet.ucla.edu
FAU - Mohammed, M
AU  - Mohammed M
FAU - Shintaku, P
AU  - Shintaku P
FAU - Rao, P N
AU  - Rao PN
LA  - eng
PT  - Journal Article
PT  - Validation Study
PL  - United States
TA  - Breast J
JT  - The breast journal
JID - 9505539
SB  - IM
MH  - Breast Neoplasms/*genetics
MH  - Chromosomes, Human, Pair 17/*genetics
MH  - Female
MH  - *Gene Amplification
MH  - Gene Expression Regulation, Neoplastic
MH  - Genes, erbB-2/*genetics
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Predictive Value of Tests
EDAT- 2002/03/22 10:00
MHDA- 2002/04/19 10:01
CRDT- 2002/03/22 10:00
PHST- 2002/03/22 10:00 [pubmed]
PHST- 2002/04/19 10:01 [medline]
PHST- 2002/03/22 10:00 [entrez]
AID - 21018 [pii]
AID - 10.1046/j.1524-4741.2001.21018.x [doi]
PST - ppublish
SO  - Breast J. 2001 Sep-Oct;7(5):337-44. doi: 10.1046/j.1524-4741.2001.21018.x.