Analysis of aneusomy level and HER-2 gene copy number and their effect on amplification rate in breast cancer specimens read as 2+ in immunohistochemical analysis.
Our aim was to determine the aneusomy level and the HER-2 gene copy numbers, by fluorescence in situ hybridization (FISH) and to analyze their impact on the amplification rate in breast carcinomas considered HER-2 weakly positive cases by immunohistochemistry. We evaluated 343 breast carcinomas using double colour FISH (LSI Her-2/neu gene and CEP 17). Monosomy and polysomy were demonstrated in 24.2% and 46.1% respectively and 101/343 (29.6%) of the specimens were amplified by FISH. A statistically significant difference was observed, when we compared the amplification percentage in polysomic and monosomic specimens (P<0.0001) and, among polysomic specimens, when tumours were compared with HER-2 gene signals number per cell between 3 and 10 and >10 respectively (P<0.0001). Logistic regression analysis showed that HER-2 signals >10 and polysomy absence were independently associated with amplification. Our results confirm that the majority of 2+ IHC cases express the HER-2 protein without gene amplification and highlight the effect of chromosome 17 aneusomy and the HER-2 gene copy number on amplification.
Merola
R
R
Department of Clinical Pathology (Cytogenetic Unit), Regina Elena Cancer Institute, Via Elio Chianesi, 53, 00144 Rome, Italy.
Mottolese
M
M
Orlandi
G
G
Vico
E
E
Cognetti
F
F
Sperduti
I
I
Fabi
A
A
Vitelli
G
G
Cianciulli
A M
AM
D001943:Breast Neoplasms / Q000235:genetics*; D002869:Chromosome Aberrations; D005784:Gene Amplification; D018628:Gene Dosage; D018734:Genes, erbB-2; D006801:Humans; D007150:Immunohistochemistry; D011003:Ploidies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D012044:Regression Analysis
D018719:Erb-b2 Receptor Tyrosine Kinases