Fluorescence In Situ Hybridization Versus Immunohistochemistry: Importance of Clinical Outcome
Authors: Steven Seelig, Timothy W. Jacobs, Stuart J. Schnitt, Allen M. Gown, Hadi Yaziji
Journal: Journal of Clinical Oncology (1999)

Article Tools Correspondence Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1999.17.11.3690 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10550171 Fluorescence In Situ Hybridization Versus Immunohistochemistry: Importance of Clinical Outcome Steven SeeligxSteven SeeligSearch for articles by this author Timothy W. JacobsxTimothy W. JacobsSearch for articles by this author , Stuart J. SchnittxStuart J. SchnittSearch for articles by this author , Allen M. GownxAllen M. GownSearch for articles by this author , Hadi YazijixHadi YazijiSearch for articles by this author Show More Vysis, Inc, Downer's Grove, ILBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MAPheonoPath Laboratories, IRIS, Seattle, WA https://doi.org/10.1200/JCO.1999.17.11.3690 First Page Full Text PDF Figures and Tables © 1999 by American Society of Clinical OncologyjcoJ Clin OncolJournal of Clinical OncologyJCO0732-183X1527-7755American Society of Clinical OncologyResponse111999In Reply: We read with interest the letter o Dr Seelig and we are pleased to have the opportunity to respond to his comments. We agree completely that there remain a number of unresolved issues regarding the most appropriate assay method for determination of the HER-2/neu status in breast cancer specimens, and our articles have highlighted some of these concerns.1,2 We also agree with Seelig's comment that at the present time, "there is insufficient information to make a decision as to whether IHC or FISH technology is better for the management of patients with breast cancer." This is related to the fact that in all of the available clinical outcome studies relating HER-2/neu status to therapeutic response, IHC was used. To our knowledge, there are as yet no published data relating HER-2/neu gene amplification as detected by FISH to response to either tamoxifen, cytotoxic therapy, or trastuzumab, although studies are currently underway to address this. Although neither our studies nor other studies published to date have completely resolved the methodologic problems with HER-2/neu analysis, we think that they have provided some data that will ultimately be of value in that regard.Seelig further suggests that to circumvent the uncertainty with regard to which assay is better, "[a]ll specimens should probably be tested with both approaches until there is sufficient information to make an intelligent decision as to the best path." We do not agree with this recommendation (outside of the setting of a research study) for a variety of reasons. First, a number of studies, including one of ours,1 have shown a high level of concordance between the two assay methods when appropriate attention is paid to technical and interpretive details of the assays. Second, although most pathology laboratories are capable of routinely performing IHC, the routine use of FISH is beyond the scope of many pathology departments. Third, the simultaneous use of both assays will result in a number of cases with discordant findings, and this will in turn create confusion with regard to clinical decision making. Fourth, Seelig notes that "IHC is a subjective technology with laboratory differences in approach to analysis and interpretation." In fact, all pathology laboratory tests, from routine hematoxylin and eosin stains to polymerase chain reaction, are subject to differences in approach to analysis and interpretation. The critical question is the degree of variation. In fact, in a recent study in which the same 100 consecutive invasive breast cancers were subjected to HER-2/neu IHC staining and interpretation in two different laboratories, there was complete concordance with regard to categorization of HER-2/neu status in 97% of the cases.3 In contrast, there are no published studies to our knowledge addressing these issues with regard to FISH. We believe that it is ill-advised to consider FISH any more accurate or reproducible than IHC until data are available to support this view. It should also be noted that Seelig's comments regarding IHC should be viewed as somewhat less than objective, since he is the Chief Medical Officer and Vice President for Research and Development for Vysis, Inc, Downer's Grove, IL, a company that is aggressively marketing a FISH probe for HER-2/neu and touting it in their advertisements as "the most accurate and reliable means of assessing HER-2/neu status in breast cancer." Fifth, another potential limitation to the use of both IHC and FISH in all cases is the increased cost associated with duplicate testing. Who is going to pay for this? Sixth, efforts are underway in both industry and the academic community to attempt to standardize IHC analysis for HER-2/neu. Although there have been concerns raised by us and others about the HercepTest (Dako Corp, Carpinteria, CA),2,4,5 we believe the development of this assay and its subsequent approval by the United States Food and Drug Administration represent important steps toward the standardization of HER-2/neu IHC, and the Dako Corporation should be commended for pursuing this important objective. Finally, in recognition of the current limitations in methods for HER-2/neu evaluation, the National Cancer Institute has organized a symposium to which experts in the fields of medical oncology, pathology, and biotechnology have been invited to discuss appropriate ways to identify patients with HER-2/neu–overexpressing malignancies. In addition, a number of cooperative groups have undertaken studies to address these lingering questions.In summary, how best to evaluate and report the HER-2/neu status of breast cancers remains a work in progress. Until the unresolved issues are resolved, pathologists and clinicians will need to determine the most appropriate method to assess the HER-2/neu status for breast cancer patients at their institutions, based upon the available data, technical considerations, and institutional expertise and resources.1. Jacobs TW, Gown AM, Yaziji H, et al: Comparison of fluorescence in situ hybridization and immunohistochemistry for the evaluation of in breast cancer. J Clin Oncol 17::1974,1999-1982, HER-2/neu Link, Google Scholar2. Jacobs TW, Gown AM, Yaziji H, et al: Specificity of HercepTest in determining status of breast cancers using the United States Food and Drug Administration–approved scoring system. J Clin Oncol 17::1983,1999-1987, HER-2/neu Link, Google Scholar3. Jacobs TW, Gown AM, Yaziji H, et al: HER2/neu protein expression in breast cancer evaluated by immunohistochemistry: A study of inter-laboratory agreement. Am J Clin Pathol (in press) Google Scholar4. Roche P, Ingle J: Increased HER2 with U.S. Food and Drug Administration–approved antibody. J Clin Oncol 17::434,1999, (letter) Link, Google Scholar5. Maia DM: Immunohistochemical assays for overexpression. J Clin Oncol 17::1650,1999, (letter)HER2 Medline, Google Scholar