Testing for erbB-2 by immunohistochemistry in breast cancer.

The success of recent clinical trials using Herceptin (trastuzumab, a humanized anti–erbB-2 antibody) as therapy for patients with advanced breast cancer 1-3 has generated a great deal of renewed interest in laboratory testing for overex-pression of the erbB-2 oncoprotein. An article by Jacobs et al 4 in this issue of the Journal describes an interesting study evaluating interlaboratory agreement in assessing overexpres-sion of erbB-2 by permanent-section immunohistochemistry (IHC). In that study, adjacent tissue sections from 93 formalin-fixed paraffin-embedded breast cancer specimens were immunostained independently in 2 very experienced laboratories. They used the same polyclonal primary anti-body but different automated immunostainers, detection systems, and methods of scoring the IHC signal. The rates of erbB-2 overexpression observed by the 2 laboratories were almost identical (23% and 24%), in line with the expected rate of 20% to 30% from many previous studies, and the agreement in interpreting cases as positive or negative for overexpression was 97%, which is remarkable. Acknowledging that it can be problematic to obtain reproducible quantitative results when assessing any biomarker by IHC, including erbB-2, one can still conclude reasonably from this study 4 that experienced laboratories using the same primary antibody and otherwise sound but somewhat dissimilar methods can obtain consistent and reasonable results when measuring overexpression of erbB-2 by IHC. One cannot conclude from this study, as the authors acknowledge, 4 that testing for erbB-2 by IHC therefore needs no further validation or standardization before becoming part of routine clinical practice. In fact, there are still large gaps in our understanding of the clinical usefulness of erbB-2 and how best to evaluate it. Because of these shortcomings, the College of American Pathologists and the American Society of Clinical Oncolo-gists do not currently recommend using erbB-2 in the routine management of patients with breast cancer. 5-7 Despite this lack of endorsement, erbB-2 is being assessed in a large proportion of breast cancers in laboratories around the world, primarily by IHC using diverse and often unproven reagents and poorly standardized methods. While this practice is open to criticism, it probably is unrealistic to expect laboratories to stop performing tests for erbB-2 until comprehensive validation is achieved (even if it is the appropriate course), especially given the substantial pressure they are under to offer them. Considerable pressure comes from patients who understandably want the latest test they hear about in the news, even though the test still may be a research …