Leica Biosystems Bond Oracle HER2 IHC System - Manual (Page 3)

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Leica Biosystems Bond Oracle HER2 IHC System Instructions for Use TA9145 EN-CE-Rev_E 18/06/2013
English
Intended Use
For in vitro diagnostic use
Bond Oracle HER2 IHC System is a semi-quantitative immunohistochemical (IHC) assay to
determine HER2 (Human Epidermal Growth Factor Receptor 2) oncoprotein status in breast
cancer tissue processed for histological evaluation. The Bond Oracle HER2 IHC System is
indicated as an aid in the assessment of patients for whom Herceptin® (trastuzumab) treatment
is being considered (see Herceptin® package insert).
Note: All of the patients in the Herceptin® clinical trials were selected using an investigational
immunocytochemical Clinical Trial Assay (CTA). None of the patients in those trials were
selected using the Bond Oracle HER2 IHC System. The Bond Oracle HER2 IHC System has
been compared to the Dako HercepTest™ on an independent set of samples and found to
provide acceptably concordant results, as indicated in the Clinical Concordance Summary.
The actual correlation of the Bond Oracle HER2 IHC System to clinical outcome has not been
established.
Summary and Explanation
Background
The Bond Oracle HER2 IHC System contains the mouse monoclonal anti-HER2 antibody, clone
CB11. Clone CB11, originally developed by Corbett et al (1) and manufactured by Novocastra
Laboratories Ltd (now Leica Biosystems Newcastle Ltd), is directed against the internal domain
of the HER2 oncoprotein.
In a proportion of breast cancer patients, the HER2 oncoprotein is overexpressed as part of the
process of malignant transformation and tumor progression (2). Overexpression of the HER2
oncoprotein found in breast cancer cells suggests HER2 as a target for an antibody-based
therapy. Herceptin® is a humanized monoclonal antibody (3) that binds with high affinity to the
HER2 oncoprotein and has been shown to inhibit the proliferation of human tumor cells that
overexpress HER2 oncoprotein both in vitro and in vivo (4–6).
Since the first immunoperoxidase technique, reported by Nakane and Pierce (7), many
developments have occurred within the field of immunohistochemistry, resulting in increased
sensitivity. A recent development has been the use of polymeric labeling. This technology has
been applied to both primary antibodies and immunohistochemical detection systems (8). The
Compact Polymer TM detection system utilized by the Bond Oracle HER2 IHC System is part of
a family of novel, controlled polymerization technologies that have been specifically developed
to prepare polymeric HRP-linked antibody conjugates. As this polymer technology is utilized in
the Oracle product range, the problem of nonspecific endogenous biotin staining, which may be
seen with streptavidin/biotin detection systems, does not occur.
Expression of HER2
The HER2 oncoprotein is expressed at levels detectable by immunohistochemistry in up to 20%
of adenocarcinomas from various sites. Between 10% and 20% of invasive ductal carcinomas
of the breast are positive for HER2 oncoprotein (9). 90% of cases of ductal carcinoma in situ
(DCIS) of comedo type are positive (10), together with almost all cases of Paget’s disease of
the breast (11).
Clinical Concordance Summary
The Bond Oracle HER2 IHC System was developed to provide an alternative to the investigational
Clinical Trial Assay (CTA) used in the Herceptin® clinical studies. The performance of the
Bond Oracle HER2 IHC System for determination of HER2 oncoprotein overexpression was
evaluated in an independent study comparing the results of the Bond Oracle HER2 IHC System
to the Dako HercepTest on 431 breast tumor specimens, of US origin. None of these tumor
specimens were obtained from patients in the Herceptin® clinical trials. The results indicated
a 92.34% concordance in a 2x2 analysis (95% confidence intervals of 89.42% to 94.67%) and
86.54% in a 3x3 analysis (95% confidence intervals of 82.95% to 89.62%) between the results
from the two assays.