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Early Detection and Diagnosis
A signature predictive of disease outcome in breast carcinomas, identified by quantitative immunocytochemical assays
Article first published online: 24 NOV 2008
Copyright © 2008 Wiley-Liss, Inc.
International Journal of Cancer
Volume 124, Issue 9, pages 2124–2134, 1 May 2009
How to Cite
Charpin, C., Secq, V., Giusiano, S., Carpentier, S., Andrac, L., Lavaut, M.-N., Allasia, C., Bonnier, P. and Garcia, S. (2009), A signature predictive of disease outcome in breast carcinomas, identified by quantitative immunocytochemical assays. Int. J. Cancer, 124: 2124–2134. doi: 10.1002/ijc.24177
- Issue published online: 24 FEB 2009
- Article first published online: 24 NOV 2008
- Manuscript Accepted: 11 NOV 2008
- Manuscript Received: 5 SEP 2008
- Institut National contre le Cancer/Canceropole Provence Alpes Côte d'Azur—AP-HM
- quantitative immunocytochemistry;
- molecular signature;
- breast cancer;
Quantitative immunocytochemical assays of 1,200 breast carcinomas were assessed after construction of tissue microarrays. A total of 42 markers were evaluated for prognostic significance by univariate log rank test (mean follow-up, 79 months), using quantitative scoring by an image analysis device and specific software. Complete data were obtained for 924 patients, for whom 27 of the 42 markers proved to be significant prognostic indicators. Analysis of these 27 markers by logistic regression showed that 18 (cMet, CD44v6, FAK, moesin, caveolin, c-Kit, CK14, CD10, P21, P27, pMAPK, pSTAT3, STAT1, SHARP2, FYN, ER, PgR and c-erb B2), and 15 when ER, PgR and c-erb B2 were excluded, were 80.52% and 78.9% predictive of disease outcome, respectively. The immunocytochemical assays on 4 micron thick sections of fixed tissue are easy to handle in current practice and are cost-effective. Quantitative densitometric measurement of immunoprecipitates by computer-assisted devices from digitized microscopic images allows standardized high-throughput “in situ” molecular profiling within tumors. It is concluded that this 15 marker immunohistochemical signature is suitable for current practice, since performed on paraffin sections of fixed tumor samples, and can be used to select patients needing more aggressive therapy, since this signature is about 80% predictive of poor clinical outcome. Also, the markers included in the signature may be indicative of tumor responsiveness to current chemotherapy or suggest new targets for specific therapies. © 2008 Wiley-Liss, Inc.