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Polysomy 17 in HER-2/neu Status Elaboration in Breast Cancer: Effect on Daily Practice

Authors' Affiliations: ¹ Pathology Department, ² Translational Research Unit, ³ Statistical Department, ⁴ Surgery Unit, and ⁵ Medical Oncology Unit, Institut J. Bordet, Brussels, Belgium and ⁶ Medical Oncology Unit, Hospital of Prato, Prato, Italy

Requests for reprints: Denis Larsimont, Department of Pathology, Institut Jules Bordet, 1 rue Heger-Bordet, 1000 Brussels, Belgium. Phone: 32-2-541-3115; Fax: 32-2-541-3281; E-mail: denis.larsimont{at}bordet.be.

Purpose: To assess the effect of chromosome 17 copy number on HER-2/neu status determination in breast cancers.

Experimental Design: HER-2/neu gene copy and chromosome 17 centromere numbers were evaluated on 893 breast carcinomas using double color fluorescence in situ hybridization (FISH). The net and chromosome 17 corrected (ratio) HER-2/neu copy numbers were compared and related to immunohistochemistry done according to the Food and Drug Administration (FDA)–approved scoring system (0, 1+, 2+, and 3+) as a first screening step in 584 cases.

Results: When a ratio 2 was considered as criterion for FISH positivity, 49.3% (440 of 893) of cases showed amplification versus 56.2% (502 of 893) by using a net HER-2/neu gene copy number >4 as a alternative criterion; 14.8% (67 of 453) of cases having a ratio <2 had a net HER-2/neu gene copy number >4 and 1.1% (5 of 440) with a ratio 2 had a net HER-2/neu gene copy number <4. Among discordant cases, 88.8% (64 of 72) were polysomic (>2.25 chromosomes 17/cell) and among polysomic cases, 12.8% (40 of 312) of the low polysomic (2.26-3.75 chromosomes 17/cell) and 36.9% (24 of 65) of the highly polysomic (>3.75 chromosomes 17/cell) cases showed discordance. In cases with a ratio <2, polysomy 17 incidences were 85.7% (6 of 7) in IHC 3+, 42.4% (79 of 186) in IHC 2+, 33.3% (15 of 45) in IHC 1+, and 29.1% (16 of 55) in IHC 0.

Conclusion: A net increase in HER-2/neu gene copy number consecutive to polysomy 17 in the absence of specific gene amplification might lead to a strong protein overexpression in a small subset of breast carcinomas. HER-2/neu status determination by FISH is dependent on the criterion considered for positivity in clinical practice.

Key Words: chromosome 17 • HER-2/neu overexpression/amplification

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