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. 2008 Oct 20;26(30):4869-74.
doi: 10.1200/JCO.2007.13.4296. Epub 2008 Sep 15.

Polysomy 17 in breast cancer: clinicopathologic significance and impact on HER-2 testing

Isabelle Vanden Bempt  1 , Peter Van Loo, Maria Drijkoningen, Patrick Neven, Ann Smeets, Marie-Rose Christiaens, Robert Paridaens, Christiane De Wolf-Peeters
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Polysomy 17 in breast cancer: clinicopathologic significance and impact on HER-2 testing

Isabelle Vanden Bempt et al. J Clin Oncol. .
Free article

Abstract

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.

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