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

Polysomy 17 in Breast Cancer: Clinicopathologic Significance and Impact on HER-2 Testing
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DOI:
10.1200/jco.2007.13.4296
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发表时间:
2008-10-20
影响因子:
45.3
通讯作者:
De Wolf-Peeters, Christiane
De Wolf-Peeters, Christiane
中科院分区:
医学1区
文献类型:
--
作者:
Vanden Bempt, Isabelle;Van Loo, Peter;De Wolf-Peeters, Christiane

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PurposePolysomy 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 MethodsIn 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.ResultsAll 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.ConclusionPolysomy 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.