Breast Center Pathology Laboratory
SERVICES/RESOURCES - CLINICAL
Prognostic Biomarkers - HER2/neu by FISH
Indications for use
The proto-oncogene HER-2/neu (c-erbB-2) resides on chromosome 17q and
encodes a trans-membrane tyrosine kinase growth factor receptor.
Amplification of the HER-2/neu gene, or overexpression of the HER-2/neu protein, is found in 20-30% of breast cancers. There is a greater
than 90% correlation between gene amplification and protein overexpression.
Some studies suggest that HER-2 gene amplification assessed by Fluorescent
In Situ Hybridization (FISH) may improve the predictive ability of
this marker for Trastuzumab (Herceptin®) therapies (1, 2), especially
in the 10-20% of cases with equivocal (i.e. 2+) results for protein
expression by IHC . The primary indication for assessing HER-2 by
FISH today is in cases with equivocal IHC results (3, 4).
Scoring/interpretation
In our laboratory, we use PathVysion, a FDA-approved kit for HER-2
testing by FISH and follow the scoring and interpretation recommended
by the manufacturer. In this procedure, the chromosome 17 centromere
is marked with a green florescent signal and HER-2 gene with an orange
florescent signal. Briefly, we assess 60 non-overlapping tumor cell
nuclei and count the number of green and orange signals in each cell.
Then, the overall gene-to-chromosome (17) ratio is calculated. A
tumor is designated as “positive” for gene amplification
if gene-to-chromosome (17) ratio is >2.0
Detailed procedure
We use FDA approved PathVysion kit to assess HER-2 by FISH. As per
manufacturers’ recommendation, 20 tumor non-overlapping cell
nuclei are enumerated to obtain the HER-2/chromosome 17 ratio.
Selected Bibliography
1. Vogel C, Cobleigh MA, Tripathy D, et al. First-line, single-agent
Herceptin(trastuzumab) in metastatic breast cancer: a preliminary
report. Eur J Cancer 37 Suppl 1:S25-9; 2001
2. Vogel CL, Cobleigh MA, Tripathy D, et al. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 20(3):719-26.; 2002
3. Roche PC, Suman VJ, Jenkins RB, et al. Concordance between local and central laboratory HER2 testing in the breast intergroup trial N9831. J Natl Cancer Inst 94(11):855-7.; 2002
4. Paik S, Bryant J, Tan-Chiu E, et al. Real-world performance of HER2 testing--ational Surgical Adjuvant Breast and Bowel Project experience. J Natl Cancer Inst 94(11):852-4.; 2002