IHC for Her2 with CBE356 antibody is a more accurate predictor of Her2 gene amplification by FISH than HercepTestTM in breast carcinoma

Abstract

Background: Her2 (c-erbB-2/neu) overexpression in breast carcinoma predicts response to the anti-Her2 monoclonal antibody, trastuzumab, and is associated with a poor prognosis. When considering patients for trastuzumab treatment, Her2 protein expression is measured by imunohistochemistry (IHC) and, where staining is equivocal, by fluorescence in situ hybridisation (FISH) detection of Her2 gene amplification. Aims: To compare IHC using CBE356 with IHC using the Food and Drug Administration approved HercepTest TM . Methods: CBE356 and HercepTest were analysed using 167 FISH characterised breast carcinomas. Immunohistochemical expression of Her2 was measured semiquantitatively. Sensitivity, specificity, predictive values, and overall accuracy were calculated for both IHC methods using gene amplification by FISH as the end point, and IHC and FISH assays were tested in Kaplan-Meier survival analysis. Results: The accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CBE356 positive (2+ and 3+) cases were 94%, 89%, 95%, 84%, and 97%, respectively, and of HercepTest positive (2+ and 3+) cases were 91%, 66%, 98%, 92%, and 91%, respectively. A positive result with CBE356, HercepTest, or FISH was associated with significantly decreased overall survival (log rank p = 0.005, p = 0.0017, and p = 0.0005, respectively). Conclusions: Positive IHC staining for Her2 using CBE356 is 3% more accurate and 23% more sensitive at predicting Her2 gene amplification by FISH than positive staining with HercepTest. Negative IHC using CBE356 antibody is 6% more likely to represent a truly negative result than negative staining with HercepTest. Overall, CBE356 was a more accurate predictor of Her2 gene amplification by FISH than HercepTest.

Immunohistochemical Antibodies in Breast Cancer HER2 Diagnostics

“…Even though our results seem to be rather inconclusive with the findings of Ainsworth et al [45] , we must admit that the antibodies driven against the extracellular domain of HER2 (CBE356 and CBE1) did not meet our expectations in this cohort of cases and we therefore cannot recommend their utilization in routine practice without profound preliminary validation.…”

Combined detection of Her2/neu gene amplification and protein overexpression in effusions from patients with breast and ovarian cancer

“…It has been described for tissue samples of breast carcinomas that staining with diVerent anti Her2/neu antibodies shows diVerent accuracy as a predictor of Her2 gene ampliWcation (Ainsworth et al 2005), and that the staining intensity of Trastuzumab is diVerent from other antibodies as was shown on cell lines and tissue samples (Glazyrin et al 2007). Therefore, we chose two antibodies directed against diVerent domains of the Her2/neu transmembrane protein: the monoclonal mouse antibody TAB 250 and the polyclonal rabbit antibody A0485.…”

Co-expression of steroid receptors (estrogen receptor alpha and/or progesterone receptors) and Her-2/neu: Clinical implications

“…One of the problems that remains with the study of Her-2/neu is its detection method(s) ( Table 3) [30][31][32][33][34][35][36][37] which has important clinical implications [32,38]. Nowadays in the clinic, immunohistochemistry is more applied than FISH, FISH is necessary when the score obtained by immunohistochemistry is 2+, and the FISH test is not necessary when the immunohistochemical scores are 0 and 1+ (negative), or 3+ (frankly positive).…”