BAG-1 Immunostaining and Survival in Early Breast Cancer
Authors: R. I. Cutress, P. A. Townsend, A. C. Bateman, P.W.M. Johnson, K. Ryder, D. M. Barnes, G. Packham, Bruce C. Turner, John C. Reed
Journal: Journal of Clinical Oncology (2001)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.16.3706 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11504752 BAG-1 Immunostaining and Survival in Early Breast Cancer R. I. CutressxR. I. CutressSearch for articles by this author , P. A. TownsendxP. A. TownsendSearch for articles by this author , A. C. BatemanxA. C. BatemanSearch for articles by this author , P.W.M. JohnsonxP.W.M. JohnsonSearch for articles by this author , K. RyderxK. RyderSearch for articles by this author , D. M. BarnesxD. M. BarnesSearch for articles by this author , G. PackhamxG. PackhamSearch for articles by this author Bruce C. TurnerxBruce C. TurnerSearch for articles by this author , John C. ReedxJohn C. ReedSearch for articles by this author Show More Southampton General Hospital, Southampton, United KingdomThomas Jefferson University, Bodine Center for Cancer Treatment, Philadelphia, PAThe Burnham Institute, Cancer Research Center, La Jolla, CA https://doi.org/10.1200/JCO.2001.19.16.3706 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical OncologyjcoJ Clin OncolJournal of Clinical OncologyJCO0732-183X1527-7755American Society of Clinical OncologyResponse15082001In Reply:The review article published in 1999 by Krajewski et al1 represented an invited report following a scientific meeting where some of our preliminary observations on expression in breast cancer of BAG-1 and several apoptosis-relevant proteins were presented by Stanislaw Krajewski, MD, PhD, in 1998. Of the 116 patients described in that 1999 review (representing patients presenting from 1973 to 1993), 42 were also part of the 122-patient cohort described in the article published in the February 15, 2001, issue of the Journal of Clinical Oncology (JCO) (patients presenting from 1978 to 1993).2The pilot immunohistochemical data described in the 1999 review1 were obtained using various anti-BAG-1 monoclonal antibodies that we were actively evaluating at that time and collectively involved use of various immunostaining methods and immunoscoring approaches, some of which had not yet been perfected. For the analysis described in our 2001 JCO article, a single monoclonal antibody was used under optimized immunostaining conditions that were quantitated by a pathologist specializing in breast cancer. A detailed protocol describing these immunostaining conditions is available on the Web at http://burnham.org/reedlab/protocols/baglimmunostain./ This monoclonal antibody is now commercially available from Dako, Inc. (Carpentiera, CA) for those wishing to reproduce our immunohistochemical analysis.In Turner et al,2 we revised our immunoscoring methods relative to the 1999 pilot report1 and also enlisted the collaborative input of a highly experienced breast pathologist who performed all of the immunoscoring (as explained in the Patients and Methods of the JCO article). Thus, the preliminary observations reported in 1999 should be viewed strictly as pilot data and do not represent a definitive analysis.In addition to important technical differences in the immunostaining and immunoscoring, data from the 1999 pilot report suggesting a correlation between nuclear BAG-1 staining and patient survival were based on 13 patients (13 of 116 were positive for nuclear BAG-1) and were not reproducible, in as much as the subsequent larger cohort published in 2001 in JCO did not reveal a significant association with survival outcome and nuclear BAG-1 staining.Regarding the question of BAG-1 and tumor histology, we mentioned in the text of Turner et al2 that no correlation was observed between BAG-1 immunostaining data and tumor grade. Tumor grade also was not statistically significantly associated with patient survival in univariate and multivariate analyses of the cohort of patients as described in our JCO article.2With respect to the question of introduction of bias in the cohort of 122 patients studied in Turner et al,2 of course, one can never entirely exclude this possibility despite best efforts. The percentage of estrogen receptor–positive cases in this cohort was indeed lower than population averages, but this population represented many young breast cancer patients (mean age, 54 years), and these patients are frequently estrogen receptor–negative. Thus, as we stated in the article, our “findings provide preliminary evidence that BAG-1 represents a potential marker of improved survival in early-stage breast cancer patients” and “larger cohorts of patients in prospective trials are needed to firmly establish the overall prognostic utility of BAG-1 testing for women with early-stage breast cancer.” Since our anti-BAG-1 monoclonal antibody is publicly available and the immunostaining method has been described in detail, we hope that others will attempt to confirm our findings in larger cohorts of patients.1. Turner B, Krajewski S, Krajewska M, et al: BAG-1: A novel biomarker predicting long-term survival in early-stage breast cancer. J Clin Oncol 19:: 992,2001-1000, Link, Google Scholar2. Krajewski S, Krajewska M, Turner B, et al: Prognostic significance of apoptosis regulators in breast cancer. Endocr Rel Cancer 6:: 29,1999-40, Crossref, Medline, Google Scholar