PURPOSE: The level of estrogen receptor (ER), progesterone receptor (PR), and HER2 aids in the determination of prognosis and treatment of breast cancer. Immunohistochemistry is currently the predominant method for assessment, but differences in methods and interpretation can substantially affect the accuracy, resulting in misclassification. Here, we investigated the association of microarray-based mRNA expression levels compared with immunohistochemistry. EXPERIMENTAL DESIGN: Microarray mRNA quantification of ER, PR, and HER2 was done by the developed TargetPrint test and compared with immunohistochemical assessment for breast tumors from 636 patients. Immunohistochemistry was done in a central laboratory and in an independent reference laboratory according to American Society of Clinical Oncology/College of American Pathologists guidelines for 100 cases. For HER2 immunohistochemistry 2+ cases, additional chromogenic in situ hybridization (CISH) was used to determine the final status. RESULTS: ER concordance between microarray and central immunohistochemistry was 93% [95% confidence interval (95% CI), 91-95%]. Only 4% of immunohistochemistry-positive samples were classified negative using microarray, whereas 18% of immunohistochemistry-negative samples showed a positive microarray ER status. Concordance for PR was 83% (95% CI, 80-86%) and 96% of all samples showed an identical classification of HER2 status by microarray and immunohistochemistry/CISH (95% CI, 94-98%). Nine percent of immunohistochemistry HER2-positive samples showed a negative microarray classification. Detailed review of 11 cases with discordant classifications by American Society of Clinical Oncology/College of American Pathologists and central immunohistochemistry indicated that microarray assessment was likely to add additional information in 5 cases. CONCLUSION: Microarray-based readout of ER, PR, and HER2 shows a high concordance with immunohistochemistry/CISH and provides an additional, objective, and quantitative assessment of tumor receptor status in breast cancer.
PURPOSE: The level of estrogen receptor (ER), progesterone receptor (PR), and HER2 aids in the determination of prognosis and treatment of breast cancer. Immunohistochemistry is currently the predominant method for assessment, but differences in methods and interpretation can substantially affect the accuracy, resulting in misclassification. Here, we investigated the association of microarray-based mRNA expression levels compared with immunohistochemistry. EXPERIMENTAL DESIGN: Microarray mRNA quantification of ER, PR, and HER2 was done by the developed TargetPrint test and compared with immunohistochemical assessment for breast tumors from 636 patients. Immunohistochemistry was done in a central laboratory and in an independent reference laboratory according to American Society of Clinical Oncology/College of American Pathologists guidelines for 100 cases. For HER2 immunohistochemistry 2+ cases, additional chromogenic in situ hybridization (CISH) was used to determine the final status. RESULTS:ER concordance between microarray and central immunohistochemistry was 93% [95% confidence interval (95% CI), 91-95%]. Only 4% of immunohistochemistry-positive samples were classified negative using microarray, whereas 18% of immunohistochemistry-negative samples showed a positive microarray ER status. Concordance for PR was 83% (95% CI, 80-86%) and 96% of all samples showed an identical classification of HER2 status by microarray and immunohistochemistry/CISH (95% CI, 94-98%). Nine percent of immunohistochemistry HER2-positive samples showed a negative microarray classification. Detailed review of 11 cases with discordant classifications by American Society of Clinical Oncology/College of American Pathologists and central immunohistochemistry indicated that microarray assessment was likely to add additional information in 5 cases. CONCLUSION: Microarray-based readout of ER, PR, and HER2 shows a high concordance with immunohistochemistry/CISH and provides an additional, objective, and quantitative assessment of tumor receptor status in breast cancer.
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