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A signature predictive of disease outcome in breast carcinomas, identified by quantitative immunocytochemical assays
Author(s) -
Charpin Colette,
Secq Véronique,
Giusiano Sophie,
Carpentier Séverine,
Andrac Lucile,
Lavaut MarieNoëlle,
Allasia Claude,
Bonnier Pascal,
Garcia Stéphane
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24177
Subject(s) - tissue microarray , immunohistochemistry , univariate analysis , pathology , medicine , log rank test , oncology , breast cancer , survival analysis , cancer , multivariate analysis
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.