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Department of Pathology, University of Southern California School of Medicine, Los Angeles, California 90033 [M. F. P., G. H.]; Division of Clinical Chemistry, Vancouver General Hospital, Vancouver, British Columbia, Canada [W. G.]; and Division of Hematology-Oncology, U.C.L.A. School of Medicine, Los Angeles, California 90024 [D. J. S.]
HER-2/neu oncogene amplification and overexpression of breast cancer tissue has been correlated with poor prognosis in women with both node-positive and node-negative disease. However, several studies have not confirmed this association. Review of these studies reveals the presence of considerable methodological variability including differences in study size, follow-up time, techniques and reagents. The majority of papers with clinical follow-up information are immunohistochemical studies using archival, paraffin-embedded breast cancers, and a variety of HER-2/neu antibodies have been used in these studies. Very little information, however, is available about the ability of the antibodies to detect overexpression following tissue processing for paraffin-embedding. Therefore, a series of antibodies, reported in the literature or commercially available, were evaluated to assess their sensitivity and specificity as immunohistochemical reagents. Paraffin-embedded samples of 187 breast cancers, previously characterized as frozen specimens for HER-2/neu amplification by Southern blot and for overexpression by Northern blot, Western blot, and immunohistochemistry, were used. Two multitumor paraffin-embedded tissue blocks were prepared from the previously analyzed breast cancers as a panel of cases to test a series of previously studied and/or commercially available anti-HER-2/neu antibodies. Immunohistochemical staining results obtained with 7 polyclonal and 21 monoclonal antibodies in sections from paraffin-embedded blocks of these breast cancers were compared. The ability of these antibodies to detect overexpression was extremely variable, providing an important explanation for the variable overexpression rate reported in the literature.
1 Supported in part by Grants CA48780, CA32737, CA36827, and CA50589 from the National Cancer Institute; Grant N01-HD-3-3175 from the National Institute of Child Health and Human Development; Grant IN-21-29/003 and PDT-411 from the American Cancer Society; the Revlon/UCLA Women's Cancer Research Program; and the Molecular Core Laboratory Facilities of the General Clinical Research Centers (National Institutes of Health National Center for Research Resources of the General Clinical Research Centers MO1 RR-43). D. J. S. has a Faculty Research Award from the American Cancer Society.
2 To whom requests for reprints should be addressed, at Department of PathologyHMR910, U.S.C. School of Medicine, 2011 Zonal Avenue, Los Angeles, CA 90033.
Received 6/ 2/93. Accepted 3/17/94.
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T. W. Jacobs, A. M. Gown, H. Yaziji, M. J. Barnes, and S. J. Schnitt Comparison of Fluorescence In Situ Hybridization and Immunohistochemistry for the Evaluation of HER-2/neu in Breast Cancer J. Clin. Oncol., July 1, 1999; 17(7): 1974 - 1974. [Abstract] [Full Text] [PDF] |
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T. W. Jacobs, A. M. Gown, H. Yaziji, M. J. Barnes, and S. J. Schnitt Specificity of HercepTest in Determining HER-2/neu Status of Breast Cancers Using the United States Food and Drug Administration-Approved Scoring System J. Clin. Oncol., July 1, 1999; 17(7): 1983 - 1983. [Abstract] [Full Text] [PDF] |
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E. Ruijter, C. van de Kaa, G. Miller, D. Ruiter, F. Debruyne, and J. Schalken Molecular Genetics and Epidemiology of Prostate Carcinoma Endocr. Rev., February 1, 1999; 20(1): 22 - 45. [Abstract] [Full Text] |
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P Nagy, A Jenei, A. Kirsch, J Szollosi, S Damjanovich, and T. Jovin Activation-dependent clustering of the erbB2 receptor tyrosine kinase detected by scanning near-field optical microscopy J. Cell Sci., January 6, 1999; 112(11): 1733 - 1741. [Abstract] [PDF] |
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J. S. Ross and J. A. Fletcher The HER-2/neu Oncogene in Breast Cancer: Prognostic Factor, Predictive Factor, and Target for Therapy Oncologist, August 1, 1998; 3(4): 237 - 252. [Abstract] [Full Text] |
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F. Revillion, L. Hornez, and J.-P. Peyrat Quantification of c-erbB-2 gene expression in breast cancer by competitive RT-PCR Clin. Chem., November 1, 1997; 43(11): 2114 - 2120. [Abstract] [Full Text] [PDF] |
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