Title: Polysomy 17 in breast cancer: clinicopathologic significance and impact on HER-2 testing
Authors: Vanden Bempt, Isabelle * ×
Van Loo, Peter *
Drijkoningen, Maria
Neven, Patrick
Smeets, Ann
Christiaens, Marie-Rose
Paridaens, Robert
Peeters, Christiane #
Issue Date: Oct-2008
Publisher: Grune & Stratton
Series Title: Journal of Clinical Oncology vol:26 issue:30 pages:4869-4874
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.
ISSN: 0732-183X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Multidisciplinary Breast Clinic Section (-)
Translational Cell & Tissue Research
Department of Human Genetics - miscellaneous
Gynaecological Oncology
Laboratory of Experimental Oncology
Human Genome Laboratory
Surgical Oncology
* (joint) first author
× corresponding author
# (joint) last author

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