Affiliation:
1. From the Department of Medicine, Division of Hematology-Oncology, University of California at Los Angeles, UCLA School of Medicine, Los Angeles, CA; and Flinders Medical Centre, Bedford Park, South Australia, Australia.
Abstract
PURPOSE: To compare the efficacy of fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) in detecting the HER-2/neu alteration in human breast cancer. PATIENTS AND METHODS: Unselected stage I, II, and III breast cancer patients (N = 900) were tested for HER-2/neu gene amplification by FISH in paraffin-embedded, formalin-fixed archival material. Of these samples, 856 were tested for HER-2/neu overexpression by non–antigen-retrieval IHC with the polyclonal antibody R60, the sensitivity and specificity of which was preliminarily compared with the United States Food and Drug Administration–approved HercepTest (Dako Corp, Carpinteria, CA). Patient survival was analyzed in relation to the presence of the HER-2/neu alteration as determined by these two methodologies. RESULTS: A total of 189 (21%) of 900 patients were positive by FISH and 147 (17.2%) of 856 were positive by IHC. This discrepancy is consistent with expected loss of IHC sensitivity associated with tissue fixation/embedding. The HercepTest did not improve sensitivity and introduced false positives. Comparison of R60-based IHC with FISH demonstrates that patient survival is associated progressively to gene amplification level as determined by FISH, whereas for IHC an association is found only in the highest (3+) immunostaining group. Among FISH-negative tumors, 45 (6.6%) of 678 were IHC-positive, with a survival probability similar to that of FISH-negative/IHC-negative cases; FISH-positive/IHC-negative patients have a survival probability similar to that of FISH-positive/IHC-positive cases. CONCLUSION: IHC does not consistently discriminate patients likely to have a poor prognosis, whereas FISH provides superior prognostic information in segregating high-risk from lower-risk beast cancers. HER-2/neu protein overexpression in the absence of gene amplification occurs infrequently in breast cancer, in which case, patient outcome is similar to that of patients without the alteration.
Publisher
American Society of Clinical Oncology (ASCO)
Reference41 articles.
1. Human Breast Cancer: Correlation of Relapse and Survival with Amplification of the HER-2/
neu
Oncogene
2. Studies of the HER-2/
neu
Proto-Oncogene in Human Breast and Ovarian Cancer
3. ERBB2 amplification in breast cancer analyzed by fluorescence in situ hybridization.
4. Pauletti G, Godolphin W, Press MF, et al: Detection and quantitation of HER-2/neu gene amplification in human breast cancer archival material using fluorescence in situ hybridization. Oncogene 13: 63,1996-72,
5. Slamon DJ, Press MF, Godolphin W, et al: The HER-2/neu proto-oncogene in human breast cancer. Cancer Cells 7: 371,1989-380,
Cited by
550 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献