Abstract
Human epidermal growth factor receptor 2 (HER2) status in breast carcinomas serves as a predictor of benefit from anti-HER2 therapy. In providing clinicians with the information necessary to decide whether or not to treat with targeted therapy, it might be necessary to choose between methods assessing HER2 protein overexpression or gene amplification. A new diagnostic approach could be a combination of both tests on the same slide. If accurate and reproducible, this approach might optimize patient stratification for therapy. In this study, formalin-fixed paraffin-embedded tumor samples from 77 breast cancer patients were examined for HER2 by immunohistochemistry (IHC) and silver in situ hybridization (SISH) using HER2 IHC (clone 4B5), HER2/CEN17SISH, and combined IHC and SISH assay, called gene protein (GP). Cases were selected to ensure a sufficient number of borderline cases on the basis of IHC scores (0, 1+, 2+, 3+), obtained during diagnostic histopathological workup. The concordance between the HER2 IHC score obtained during diagnostic histopathological workup and GP was 93 %. Discordances had no influence on therapy decisions. The concordance between ISH results using dual ISH (DISH) and GP was 96 %. Of the 77 cases studied by GP, three cases with a ratio close to 2 would have been called amplified by DISH. The use of GP reduced the time for slide reading for a trained pathologist by up to 25 %, relative to sequential reading of IHC followed by SISH. For cases with an IHC score of 2+, the final result was obtained in 1 day, while the sequential technique would have required retesting by ISH on a second day. In conclusion, assessment of HER2 status by GP is an improvement for pathologists and facilitates clinical decision-making for breast cancer management.
Highlights
Human epidermal growth factor receptor 2 (HER2) is a protein on the surface of cancer cells that stimulates tumor growth
The first impression when looking at gene protein (GP)-stained slides was that immunostaining is less crisp, which might be due to the pretreatment required for the dual in situ hybridization (ISH) (DISH) step
This had no impact on reading or scoring, following American Society of Clinical Oncology (ASCO)-CAP 2007 or the recently published ASCO-CAP 2013 guidelines, reading GP-stained slides might require some time for an experienced pathologist to adapt (Fig. 1)
Summary
Human epidermal growth factor receptor 2 (HER2) is a protein on the surface of cancer cells that stimulates tumor growth. When the HER2 gene is amplified, it triggers overproduction, commonly called overexpression, of HER2 [1] protein. Tumors that strongly overexpress HER2 and/or those with a proven amplification of the HER2 gene are classified as being HER2 positive. In the early days of HER2 testing, amplification of the HER2 gene and the corresponding overexpression of HER2 protein was found in approximately 25 to 30 % of breast cancer [5], but this rate was probably an overestimate as it is identified in approximately 15 to 20 % [6] of primary breast cancer cases, while recent data show a further decreasing trend to around 14 % [7]
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