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Identification of Overexpression and Amplification of ABCF2 in Clear Cell Ovarian Adenocarcinomas by cDNA Microarray Analyses

Authors' Affiliations: Departments of ¹ Obstetrics and Gynecology, Laboratory of Gynecologic Oncology, and ² Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; ³ Department of Obstetrics and Gynecology, Osaka City General Hospital, Osaka, Japan; ⁴ Cell and Cancer Biology Branch, National Cancer Institute, Bethesda, Maryland; ⁵ Department of Biostatistics/Epidemiology and Preventive Health Science, School of Health Sciences and Nursing, University of Tokyo, Tokyo, Japan; and ⁶ Laboratory of Molecular Cytogenetics, Department of Gynecologic Oncology, M.D. Anderson Cancer Center, Houston, Texas

Requests for reprints: Samuel C. Mok, Laboratory of Gynecologic Oncology, Brigham and Women's Hospital, BLI-447, 221 Longwood Avenue, Boston, MA 02115. Phone: 617-278-0196; Fax: 617-975-0818; E-mail: scmok{at}rics.bwh.harvard.edu.

Purpose: Patients with ovarian clear cell adenocarcinoma generally have a poor response to combination chemotherapy and have overall poorer prognosis than patients with other histologic types of ovarian cancer. Genetic changes in this group of cancer have not been thoroughly explored. Identification of these changes may provide us new therapeutic targets to treat this disease.

Experimental Design: Genomic and expression array analyses were applied on 30 clear cell ovarian cancer cases and 19 serous cases using a 10,816-element cDNA microarray platform. Further validation and clinical correlation studies were done on differentially expressed genes that are related to chemoresistance.

Results: Based on array analyses, 12 genes showed a significant increase in DNA and mRNA copy number and 5 genes showed a significant decrease in DNA and RNA copy number in clear cell tumors compared with those in the serous type. One of the genes was ABCF2, which belongs to the ATP-binding cassette gene superfamily and has been shown to amplify in other tumor types. Validation studies were done using real-time quantitative PCR and immunohistochemistry. The results showed significantly higher ABCF2 DNA and mRNA copy number and protein levels in clear cell cases compared with those in serous cases. Furthermore, in 20 clear cell cases with chemoresponse data available, ABCF2 cytoplasmic staining was significantly higher in nonresponders than that in the responders (60.0% versus 28.5%; P = 0.0002).

Conclusions: These data suggest that ABCF2 protein may be a prognostic marker for ovarian clear cell ovarian adenocarcinoma.

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