HER-2/neu protein expression and gene amplification in breast cancer: immunohistochemistry and chromogenic in situ hybridization study using tissue microarray

Breast cancer is the most prevalent cancer in women worldwide, second only to skin cancer. The assessment of HER-2/neu status is crucial in managing breast cancer patients. The objectives of this study were to determine the sensitivity and specificity of immunohistochemistry (IHC) compared to chromogenic in situ hybridization (CISH) in assessment of HER-2/neu status in breast cancer tissues, and to assess the reliability of tissue microarray (TMA) for IHC and CISH techniques. One hundred twenty seven histologically confirmed breast cancer cores in tissue microarrays were tested by IHC and CISH. HER-2/neu overexpression and gene amplification were assessed using HercepTest T and Zyto Dot SPEC HER2 Probe Kit respectively. IHC staining and HER-2/neu signals on TMA were clear and easy to interpret. Positive IHC results for HER-2/neu were detected in 22% of cancers, while HER-2/neu gene amplification was seen in 43.3% of cancer cases. All 3+ IHC cases showed HER-2/neu gene amplification, with a highly significant correlation between IHC and CISH (p<.001). The sensitivity and specificity of IHC in predicting HER-2/neu amplification were 44.6% and 95.8% respectively. Our findings verified a high likelihood of breast cancers harboring HER-2/neu gene amplification in the absence of HER-2/neu oncoprotein expression. Therefore, we recommend CISH as a useful test in confirming IHC results for HER-2/neu status. Moreover, TMA appears to be a highly reliable, standardized and a cost effective method for performing IHC and CISH.