Abstract

Abstract Background: Recent clinical validation of a commercially available array CGH test (HerScan™) for determination of HER2 status in 97 cases of newly diagnosed breast cancer showed high accuracy and 97% concordance with fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) results meeting the CAP/ASCO validation requirements for HER2 testing. However, the validation study was performed using fresh frozen tissue, a requirement which precludes the clinical use of array CGH in the majority of breast cancer workups. In this study, 55 additional cases with known HER2 status by IHC and FISH were analyzed by array CGH using a tumor-targeted DNA extraction method designed to achieve optimal results from formalin fixed paraffin embedded (FFPE) tissue.Methods: Tumor tissue from 55 cases of invasive ductal, invasive lobular, and one mucinous carcinoma was visualized and marked on H&E stained sections cut from the FFPE block, with targeted areas captured by slide scraping or 4mm punch. Following proteinase K digestion, DNA was extracted from known HER2 positive (n=25), HER2 negative (n=25), and HER2 equivocal (n=5) samples. Verification of high molecular weight DNA was accomplished by agarose gel electropheresis followed by analysis of the tumor genomes using the HerScan test, a 1524 clone whole genome BAC microarray including 64 probes targeting the HER2/TOP2A amplicons on chromosome 17q.Results: Concordance equivalent to fresh frozen tissue results (>95%) was found between HER2 status obtained by IHC/FISH and array CGH on FFPE tissue. Five cases with equivocal results by IHC/FISH were resolved by array CGH and found to have unamplified partial chromosome 17 polysomy (n=4) and normal HER2 status (n=1). In addition, chromosome 17 status, overall genomic stability, and the presence of co-amplified genes including EGFR, MYC, MDM2, CCND1, and PDGFRalpha were clearly revealed by microarray evaluation in all cases.Conclusions: Array CGH analysis of DNA extracted from FFPE tissue provides a robust and accurate alternative for the clinical determination of HER2 status in newly diagnosed breast cancer. In addition, the complete genomic evaluation of core biopsy specimens afforded by array CGH allows clinicians to deliver personalized cancer care through incorporation of prognostic markers and potential therapeutic targets into treatment planning and prediction of disease outcome. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6038.

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