PMID- 20667129
OWN - NLM
STAT- MEDLINE
DCOM- 20110203
LR  - 20211020
IS  - 1471-2407 (Electronic)
IS  - 1471-2407 (Linking)
VI  - 10
DP  - 2010 Jul 28
TI  - Clinical array-based karyotyping of breast cancer with equivocal HER2 status 
      resolves gene copy number and reveals chromosome 17 complexity.
PG  - 396
LID - 10.1186/1471-2407-10-396 [doi]
AB  - BACKGROUND: HER2 gene copy status, and concomitant administration of trastuzumab 
      (Herceptin), remains one of the best examples of targeted cancer therapy based on 
      understanding the genomic etiology of disease. However, newly diagnosed breast 
      cancer cases with equivocal HER2 results present a challenge for the oncologist 
      who must make treatment decisions despite the patient's unresolved HER2 status. 
      In some cases both immunohistochemistry (IHC) and fluorescence in situ 
      hybridization (FISH) are reported as equivocal, whereas in other cases IHC 
      results and FISH are discordant for positive versus negative results. The recent 
      validation of array-based, molecular karyotyping for clinical oncology testing 
      provides an alternative method for determination of HER2 gene copy number status 
      in cases remaining unresolved by traditional methods. METHODS: In the current 
      study, DNA extracted from 20 formalin fixed paraffin embedded (FFPE) tissue 
      samples from newly diagnosed cases of invasive ductal carcinoma referred to our 
      laboratory with unresolved HER2 status, were analyzed using a clinically 
      validated genomic array containing 127 probes covering the HER2 amplicon, the 
      pericentromeric regions, and both chromosome 17 arms. RESULTS: Array-based 
      comparative genomic hybridization (array CGH) analysis of chromosome 17 resolved 
      HER2 gene status in [20/20] (100%) of cases and revealed additional chromosome 17 
      copy number changes in [18/20] (90%) of cases. Array CGH analysis also revealed 
      two false positives and one false negative by FISH due to "ratio skewing" caused 
      by chromosomal gains and losses in the centromeric region. All cases with complex 
      rearrangements of chromosome 17 showed genome-wide chromosomal instability. 
      CONCLUSIONS: These results illustrate the analytical power of array-based genomic 
      analysis as a clinical laboratory technique for resolution of HER2 status in 
      breast cancer cases with equivocal results. The frequency of complex chromosome 
      17 abnormalities in these cases suggests that the two probe FISH interphase 
      analysis is inadequate and results interpreted using the HER2/CEP17 ratio should 
      be reported "with caution" when the presence of centromeric amplification or 
      monosomy is suspected by FISH signal gains or losses. The presence of these 
      pericentromeric copy number changes may result in artificial skewing of the 
      HER2/CEP17 ratio towards false negative or false positive results in breast 
      cancer with chromosome 17 complexity. Full genomic analysis should be considered 
      in all cases with complex chromosome 17 aneusomy as these cases are likely to 
      have genome-wide instability, amplifications, and a poor prognosis.
FAU - Gunn, Shelly
AU  - Gunn S
AD  - Combimatrix Molecular Diagnostics, 310 Goddard, Irvine, California 92618, USA. 
      gunn@uthscsa.edu
FAU - Yeh, I-Tien
AU  - Yeh IT
FAU - Lytvak, Irina
AU  - Lytvak I
FAU - Tirtorahardjo, Budi
AU  - Tirtorahardjo B
FAU - Dzidic, Natasha
AU  - Dzidic N
FAU - Zadeh, Soheila
AU  - Zadeh S
FAU - Kim, Jaeweon
AU  - Kim J
FAU - McCaskill, Chris
AU  - McCaskill C
FAU - Lim, Lony
AU  - Lim L
FAU - Gorre, Mercedes
AU  - Gorre M
FAU - Mohammed, Mansoor
AU  - Mohammed M
LA  - eng
PT  - Journal Article
DEP - 20100728
PL  - England
TA  - BMC Cancer
JT  - BMC cancer
JID - 100967800
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Breast Neoplasms/*genetics/pathology
MH  - Carcinoma, Ductal, Breast/*genetics/pathology
MH  - *Chromosome Aberrations
MH  - Chromosomes, Human, Pair 17/*genetics
MH  - Comparative Genomic Hybridization
MH  - Female
MH  - *Gene Dosage
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Karyotyping
MH  - *Oligonucleotide Array Sequence Analysis
MH  - Receptor, ErbB-2/*genetics
PMC - PMC2915985
EDAT- 2010/07/30 06:00
MHDA- 2011/02/04 06:00
PMCR- 2010/07/28
CRDT- 2010/07/30 06:00
PHST- 2010/03/06 00:00 [received]
PHST- 2010/07/28 00:00 [accepted]
PHST- 2010/07/30 06:00 [entrez]
PHST- 2010/07/30 06:00 [pubmed]
PHST- 2011/02/04 06:00 [medline]
PHST- 2010/07/28 00:00 [pmc-release]
AID - 1471-2407-10-396 [pii]
AID - 10.1186/1471-2407-10-396 [doi]
PST - epublish
SO  - BMC Cancer. 2010 Jul 28;10:396. doi: 10.1186/1471-2407-10-396.