title: A signature predictive of disease outcome in breast carcinomas, identified by quantitative immunocytochemical assays.
abstract: 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.
authors.affiliation: Department of Pathology, Hôpital Nord and Université de la Méditerranée (Aix Marseille II), Marseille, France. colette.charpin@ap-hm.fr
authors.forename: Colette
authors.initials: C
authors.lastname: Charpin
authors.forename: Véronique
authors.initials: V
authors.lastname: Secq
authors.forename: Sophie
authors.initials: S
authors.lastname: Giusiano
authors.forename: Séverine
authors.initials: S
authors.lastname: Carpentier
authors.forename: Lucile
authors.initials: L
authors.lastname: Andrac
authors.forename: Marie-Noëlle
authors.initials: MN
authors.lastname: Lavaut
authors.forename: Claude
authors.initials: C
authors.lastname: Allasia
authors.forename: Pascal
authors.initials: P
authors.lastname: Bonnier
authors.forename: Stéphane
authors.initials: S
authors.lastname: Garcia
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000556:secondary / Q000601:surgery; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D012372:ROC Curve; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor