Polysomy 17 in HER-2/neu status elaboration in breast cancer: effect on daily practice.
OBJECTIVE
To assess the effect of chromosome 17 copy number on HER-2/neu status determination in breast cancers.


METHODS
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 > or = 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 > or = 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.


CONCLUSIONS
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.
Ma
Yan
Y
Pathology Department, Institut Jules Bordet, Brussels, Belgium.
Lespagnard
Laurence
L
Durbecq
Virginie
V
Paesmans
Marianne
M
Desmedt
Christine
C
Gomez-Galdon
Maria
M
Veys
Isabelle
I
Cardoso
Fatima
F
Sotiriou
Christos
C
Di Leo
Angelo
A
Piccart
Martine J
MJ
Larsimont
Denis
D
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000235:genetics*
D018719:Erb-b2 Receptor Tyrosine Kinases