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[Cancer Research 65, 10602-10612, November 15, 2005]
© 2005 American Association for Cancer Research

Clinical Research

Expression Profiling of Serous Low Malignant Potential, Low-Grade, and High-Grade Tumors of the Ovary

Tomas Bonome1, Ji-Young Lee2, Dong-Choon Park2, Mike Radonovich1, Cindy Pise-Masison1, John Brady1, Ginger J. Gardner1, Ke Hao3, Wing H. Wong4, J. Carl Barrett1, Karen H. Lu5, Anil K. Sood5, David M. Gershenson5, Samuel C. Mok2 and Michael J. Birrer1

1 Cell and Cancer Biology Branch, National Cancer Institute, Bethesda, Maryland; 2 Laboratory of Gynecologic Oncology, Brigham and Women's Hospital, Harvard Medical School; 3 Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts; 4 Department of Statistics, Stanford University, Stanford, California; and 5 Department of Gynecologic Oncology, M.D. Anderson Cancer Center, Houston, Texas

Requests for reprints: Michael J. Birrer, Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, 9000 Rockville Pike 37/1130, Bethesda, MD 20892. Phone: 301-402-9586; Fax: 301-480-4756; E-mail: birrerm{at}bprb.nci.nih.gov.

Papillary serous low malignant potential (LMP) tumors are characterized by malignant features and metastatic potential yet display a benign clinical course. The role of LMP tumors in the development of invasive epithelial cancer of the ovary is not clearly defined. The aim of this study is to determine the relationships among LMP tumors and invasive ovarian cancers and identify genes contributing to their phenotypes. Affymetrix U133 Plus 2.0 microarrays (Santa Clara, CA) were used to interrogate 80 microdissected serous LMP tumors and invasive ovarian malignancies along with 10 ovarian surface epithelium (OSE) brushings. Gene expression profiles for each tumor class were used to complete unsupervised hierarchical clustering analyses and identify differentially expressed genes contributing to these associations. Unsupervised hierarchical clustering analysis revealed a distinct separation between clusters containing borderline and high-grade lesions. The majority of low-grade tumors clustered with LMP tumors. Comparing OSE with high-grade and LMP expression profiles revealed enhanced expression of genes linked to cell proliferation, chromosomal instability, and epigenetic silencing in high-grade cancers, whereas LMP tumors displayed activated p53 signaling. The expression profiles of LMP, low-grade, and high-grade papillary serous ovarian carcinomas suggest that LMP tumors are distinct from high-grade cancers; however, they are remarkably similar to low-grade cancers. Prominent expression of p53 pathway members may play an important role in the LMP tumor phenotype.




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