Originally published as JCO Early Release 10.1200/JCO.2005.02.9363 on October 3 2005

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Unique Gene Expression Profile Based on Pathologic Response in Epithelial Ovarian Cancer

From the Program of Gynecologic Medical Oncology, Beth Israel Deaconess Medical Center, Genomics Center and Bioinformatics Core, Beth Israel Deaconess Medical Center, Harvard Medical School, and the Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY

Address reprint requests to Stephen A. Cannistra, Program of Gynecologic Medical Oncology, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215; e-mail: scannist{at}bidmc.harvard.edu

PURPOSE: We investigated whether tumor tissue obtained at diagnosis expresses a specific gene profile that is predictive of findings at second-look surgery in patients with epithelial ovarian cancer (EOC).

PATIENTS AND METHODS: Tumor tissue obtained at the time of diagnosis was profiled with oligonucleotide microarrays. Class prediction analysis was performed in a training set of 24 patients who had undergone a second-look procedure. The resultant predictive signature was then tested on an independent validation set comprised of 36 patients.

RESULTS: A 93-gene signature referred to as the Chemotherapy Response Profile (CRP) was identified through its association with pathologic complete response. When applied to a separate validation set, the CRP distinguished between patients with unfavorable versus favorable overall survival (median 41 months v not yet reached, respectively, log-rank P = .007), with a median follow-up of 52 months. The signature maintained independent prognostic value in multivariate analysis, controlling for other known prognostic factors such as age, stage, grade, and debulking status. There was no genetic overlap between the CRP and our previously described Ovarian Cancer Prognostic Profile (OCPP), which demonstrated similar prognostic value. The combination of the CRP and OCPP yielded better prognostic discrimination then either profile alone. Genes present in the CRP include BAX, a proapoptotic protein previously associated with chemotherapy response in ovarian cancer.

CONCLUSION: Identification of a gene expression profile based on pathologic response in EOC provides independent prognostic information and offers potential insights into the mechanism of drug resistance. Efforts to identify a more tailored profile using selected genes from both the CRP and OCPP are underway.

Supported in part through grants from the Paul Weisman Fund, the Ovarian Cancer SPORE (P50 CA105009, Career Development Award), 1R21CA107352, and the Director's Challenge Grant (U01 CA88175), RO1 CA85467, and U24 DK58739.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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