Determination of HER-2/neu status has thus taken on great importance in the routine work-up of breast cancer in the pathology laboratory:over-expression of the protein product of HER-2/neu gene is usually a direct consequence of gene amplification, in which multiple copies of the gene appear throughout the genome. The two most widely used technologies are immunohistochemistry (IHC) and FISH, because these two techniques are ideal for use on paraffin embedded tissue, including archival material. FISH is considered the gold standard for HER2 assessment and correlates best with outcome and response to traztuzamab treatment.While FISH detects gene amplification, IN+HC detects gene product overexpression.
The technology used is Vysis Pathvysion, with the result of amplification of HER in ration of >2.2:1. According to the test makers (http://www.abbottmolecular.com/PathVysionHER2DNAProbeKit_5138.aspx), specimens with amplification showed a LSI HER-2/neu and CEP 17 signal ratio of greater than or equal to 2.0; normal specimens showed a ratio of less than 2.0. Results at or near the cut-off point (1.8-2.2) should be interpreted with caution. I understand this to mean that this is an equivocal HER test.
It is not known how to deal with equivocal FISH results. The ASCO/CAP guidelines and the PathVysion HER-2 DNA Probe Kit package insert recommend counting additional cells as a step toward resolving equivocal HER2 amplification status. However it does not always resolve the issue and exposing a patient to year of Herceptin in such a situation would be considered experimental.
As an unproven treatment, Herceptin in this situation should be considered not med. necessary when HER/2Neu test is equivocal.
Bast RC Jr, Ravdin P, Hayes DF, et al. 2000 update of recommendations for the use of tumor markers in breast and colorectal cancer: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol. 2001;19:1865-1878.
- Carlson RW, Moench SJ, Hammond ME, et al. HER2 testing in breast cancer: NCCN Task Force report and recommendations. J Natl Compr Canc Netw. 2006;4(suppl 3):S1-S24.
- Wolff AC, Hammond ME, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 2007;25:118-145. 2013 Update: http://www.cancer.net/publications-and-resources/asco-care-and-treatment-recommendations-patients/her2-testing-breast-cancer