Originally published as JCO Early Release 10.1200/JCO.2007.13.4296 on September 15 2008

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Polysomy 17 in Breast Cancer: Clinicopathologic Significance and Impact on HER-2 Testing

Isabelle Vanden Bempt, Peter Van Loo, Maria Drijkoningen, Patrick Neven, Ann Smeets, Marie-Rose Christiaens, Robert Paridaens, Christiane De Wolf-Peeters

From the Departments of Pathology, Obstetrics and Gynecology, Surgery-Senology, and General Medical Oncology and Multidisciplinary Breast Centre, University Hospital Gasthuisberg, and Departments of Human Genetics and Electrical Engineering, Katholieke Universiteit Leuven; and Department of Molecular and Developmental Genetics, Flanders Institute for Biotechnology, Leuven, Belgium

Corresponding author: Isabelle Vanden Bempt, PhD, Department of Pathology, Minderbroedersstraat 12, 3000 Leuven, Belgium; e-mail: isabelle.vandenbempt{at}uz.kuleuven.ac.be

Purpose Polysomy 17 is frequently found in breast cancer and may complicate the interpretation of HER-2 testing results. We investigated the impact of polysomy 17 on HER-2 testing and studied its clinicopathologic significance in relation to HER2 gene amplification.

Patients and Methods In 226 patients with primary invasive breast carcinoma, HER2 gene and chromosome 17 copy numbers were determined by dual-color fluorescent in situ hybridization (FISH). The interpretation of FISH results was based on either absolute HER2 gene copy number or the ratio HER2/chromosome 17. Results were correlated with HER-2 protein expression on immunohistochemistry (IHC), HER2 mRNA expression by reverse transcriptase polymerase chain reaction (RT-PCR), and with various clinicopathologic parameters.

Results All cases with an equivocal HER-2 result by FISH, either by absolute HER2 copy number (44 of 226 patients; 19.5%) or by the ratio HER2/chromosome 17 (three of 226 patients; 1.3%), displayed polysomy 17. On its own, polysomy 17 was not associated with HER-2 overexpression on IHC or increased HER2 mRNA levels by RT-PCR. Moreover, and in contrast with HER2 gene amplification, polysomy 17 was not associated with high tumor grade, hormone receptor negativity, or reduced disease-free survival.

Conclusion Polysomy 17 affects HER-2 testing in breast cancer and is a major cause of equivocal results by FISH. We show that tumors displaying polysomy 17 in the absence of HER2 gene amplification resemble more HER-2–negative than HER-2–positive tumors. These findings highlight the need for clinical trials to investigative whether polysomy 17 tumors benefit from HER-2–targeted therapy.

published online ahead of print at www.jco.org on September 15, 2008.

I.V.B. and P.V.L. contributed equally to this work.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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  JCO 2008 26: 4856-4858 [Full Text]

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