Resolution of HER2 STATUS in Breast Cancer Cases with Equivocal IHC Scores Using a Clinically Validated Array CGH Test for Chromosome 17 Analysis
I Lytvak, SR Gunn, IT Yeh. University of Texas Health Science Center, San Antonio, TX
Background: Recent multi-probe FISH and array CGH studies have shown that the co-existence of pericentromeric chromosome 17 amplification and HER2 positivity can result in a false negative HER2/cep17 ratio in newly diagnosed breast cancer. This previously unsuspected complexity of chromosome 17 in many breast cancer cases has resulted in a need for the development of alternative methods for resolution of HER2 status. Recent validation of commercially available array CGH tests for analysis of the breast cancer genome provide an alternative high throughput method for accurate determination of HER2 gene copy number and chromosome 17 status. In the current study 20 cases of IHC 2+ invasive ductal carcinoma were analyzed by array CGH for the resolution of HER2 and chromosome 17 status.
Design: Tumor targeted DNA extraction was performed on fresh frozen tumor tissue from 20 cases of invasive ductal carcinoma with IHC scores of 2+. Chromosome 17 analysis was performed using the Her17Scan™ test, a whole genome BAC microarray with 127 probe coverage of chromosome 17 including specific targeting of the pericentormeric region and the HER2/TOP2A amplicons.
Results: HER2 gene copy number and chromosome 17 status were resolved in all cases. 18 cases were HER2 negative and 2 cases were HER2 positive by array CGH. HER2 negative cases showed a marked heterogeneity of chromosome 17 structure. The majority displayed a complex pattern of gains and losses of genetic material on both q and p arms, but with no change in the centromeric region.Four cases showed completely normal chromosome 17. One case demonstrated significant gain of genetic material on both arms of chromosome 17 with associated amplification of pericentromeric region. All cases negative for HER2 by array CGH were also HER2 negative by FISH. 2 cases showed amplification of HER2 by array CGH. Complex abnormalities of chromosome 17 were identified including significant gain of genetic material on both arms in one case and multiple gains and losses in another case; no changes in the centromeric region was identified in this group. FISH confirmed HER2 amplification in both these cases.
Conclusions: Array CGH is a robust technique for determination of HER2 and chromosome 17 status in newly diagnosed breast cancer. This test enables evaluation of the entire chromosome 17 thus providing the clinician with additional information that may affect treatment strategies and prognosis.
Monday, March 22, 2010 9:00 AM
Platform Session: Section G 1, Monday Morning