There are currently three tissue-based diagnostics available to test for HER-2 positive breast cancer:

  • Immunohistochemistry
  • Inform Dual In Situ Hybridization
  • Fluorescence In Situ Hybridization

Pathologists use HER-2 tissue tests to detect a protein called HER-2 (“human epidermal growth factor receptor 2”) that is found in certain types of cancer cells.   Alternatively, some tests are designed to detect the HER-2 gene that produces the protein. HER-2 tests are used to determine whether the tumor has too much of the HER-2 protein or too many copies of its gene.

All of the tests involve taking a small piece of tissue from a breast tumor, but they are different in the ways they detect HER-2 and the kinds of results they provide. These differences are outlined below:

Immunohistochemistry (IHC)1

IHC is performed on fresh or frozen biopsy material. It gives four possible results ranging from 0 to 3+ to determine whether there is too much HER-2 protein in the cancer cells. A result of 0 or 1+ indicates there is no excess, 2+ is borderline, and 3+ means the cells test positive for an overexpression of the HER-2 protein. That is, there is too much HER-2 on the surface of the cancer cells.

A pathologist will use a stain to mark the HER-2 proteins on the cell. They will then use a specialized microscope to visualize the results and measure the amount of HER-2 on the outside of the cell. These observations are translated into a score, which is given as the result. If you have an IHC 2+ result, your doctor may send you for one of the other, more accurate tests to be certain of your HER-2 status.

Inform HER-2 Dual In Situ Hybridization (Inform HER-2 Dual ISH) 2

Inform HER-2 Dual ISH is similar to IHC in that it tests for HER-2 proteins in breast cancer cells. It can be performed on biopsies that have been stored in chemicals or wax. Essentially, it is a stain that colors the proteins on the cells. In this way, pathologists can determine whether the HER-2 protein is present by using a microscope to see the newly colored proteins. Tests results will either be “positive” or “negative” for HER-2. Compared to FISH, Inform HER-2 Dual is both more cost effective and more accurate.

Related:  Monitoring Serum HER2 for Breast Cancer Prognosis

Fluorescence In Situ Hybridization (FISH) 3

The FISH test is also performed on biopsy material, preferably fresh or preserved in wax, and will give a result of either “positive” or “negative”. It is used to identify particular genes within a person’s cells. In this case, the FISH test actually highlights the HER-2 gene on the chromosomes of the breast cancer cells. Recalling from above, a gene makes a protein. Therefore, if breast cancer cells have too many HER-2 genes, they may also be overexpressing HER-2 proteins.

FISH is considered a gold standard test that is often used in conjunction with other tests like IHC to provide patients and physicians a more accurate staging of HER-2 status.

  1. Dendukuri, N. (2007) “Testing for HER2-positive breast cancer: a systematic review and cost-effectiveness analysis”, Canadian Medical Association Journal, 176(10) (pp. 1429-1434).
  1. Breast (2013) “Inform HER2 Dual ISH Test” Accessed at:
  1. Breast (2012) “FISH Test (Fluorescence In Situ Hybridization)” Accessed at:
  1. Zhao, J. (2002) “Determination of HER2 gene amplification by chromogenic in situ hybridization (CISH) in archival breast carcinoma”, Modern Pathology, 15(6) (pp. 657-65).
  1. Tanner, M. (2000) “Chromogenic in Situ Hybridization”, The American Journal of Pathology, 15(5) (pp. 1467-1472).