Determination of HER-2 status and chromosome 17 polysomy in breast carcinomas comparing HercepTest and PathVysion FISH assay.
We evaluated and compared 2 HER-2 tests (immunohistochemical analysis [HercepTest, DAKO, Carpinteria, CA] and fluorescence in situ hybridization [FISH]) and assessed chromosome 17 polysomy status in relation to these tests. HER-2 status was obtained in 690 cases. The rinse step in the HercepTest before and after addition of the visualization reagent was 2 minutes in 188 cases and was increased to 5 minutes in 600 cases. HercepTest with both rinse steps was performed on duplicate slides in 98 cases. Chromosome 17 ploidy status based on FISH results was determined in 687 cases. Weak overexpression (2+) of HER-2 protein was not due to gene amplification in a majority of cases (67/76 [88%]). A small subset of breast carcinomas (19/687 [2.8%]) strongly overexpressed (3+) HER-2 protein without gene amplification. The aneuploidy rate was similar in negative and 2+ cases (60/141 [42.5%] and 12/26 [46%]), compared with 86% (18/21) in 3+ cases. The incidence of polysomy 17 in 2+ nonamplified cases (3/67 [4%]) was similar to that seen in negative cases (5.5%), in contrast with 47% (9/19) of 3+ nonamplified cases. Adding a longer rinse step to the HercepTest converted a subset (3/10 [30%]) of weakly positive cases to negative cases. Weak overexpression of HER-2 protein in a majority of cases seems to represent an artifactual staining pattern. Chromosome 17 polysomy is a major factor in strong HER-2 protein overexpression in 3+ nonamplified cases.
Varshney
Dolly
D
Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Zhou
Yvonne Y
YY
Geller
Stephen A
SA
Alsabeh
Randa
R
D000782:Aneuploidy; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002886:Chromosomes, Human, Pair 17; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D011933:Reagent Kits, Diagnostic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism
D004273:DNA, Neoplasm; D011933:Reagent Kits, Diagnostic; D018719:Erb-b2 Receptor Tyrosine Kinases