Expression profiling of serous low malignant potential, low-grade, and high-grade tumors of the ovary.

被引:240
作者
Bonome, T
Lee, JY
Park, DC
Radonovich, M
Pise-Masison, C
Brady, J
Gardner, GJ
Hao, K
Wong, WH
Barrett, JC
Lu, KH
Sood, AK
Gershenson, DM
Mok, SC
Birrer, MJ
机构
[1] NCI, Cell & Canc Biol Branch, Canc Res Ctr, Bethesda, MD 20892 USA
[2] Harvard Univ, Sch Med, Brigham & Womens Hosp, Lab Gynecol Oncol, Boston, MA 02115 USA
[3] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA
[4] Stanford Univ, Dept Stat, Stanford, CA 94305 USA
[5] Univ Texas, MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA
关键词
D O I
10.1158/0008-5472.CAN-05-2240
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:10602 / 10612
页数:11
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