Bonome Tomas, Lee Ji-Young, Park Dong-Choon, Radonovich Mike, Pise-Masison Cindy, Brady John, Gardner Ginger J, Hao Ke, Wong Wing H, Barrett J Carl, Lu Karen H, Sood Anil K, Gershenson David M, Mok Samuel C, Birrer Michael J
Cell and Cancer Biology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA.
Cancer Res. 2005 Nov 15;65(22):10602-12. doi: 10.1158/0008-5472.CAN-05-2240.
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.
浆液性乳头状低恶性潜能(LMP)肿瘤具有恶性特征和转移潜能,但临床病程呈良性。LMP肿瘤在卵巢浸润性上皮癌发生中的作用尚未明确界定。本研究的目的是确定LMP肿瘤与卵巢浸润性癌之间的关系,并鉴定促成其表型的基因。使用Affymetrix U133 Plus 2.0微阵列(加利福尼亚州圣克拉拉)对80个经显微切割的浆液性LMP肿瘤、卵巢浸润性恶性肿瘤以及10个卵巢表面上皮(OSE)刷检样本进行检测。利用每个肿瘤类别的基因表达谱完成无监督层次聚类分析,并鉴定促成这些关联的差异表达基因。无监督层次聚类分析显示,包含交界性和高级别病变的簇之间有明显区分。大多数低级别肿瘤与LMP肿瘤聚类在一起。将OSE与高级别和LMP表达谱进行比较发现,与细胞增殖、染色体不稳定和表观遗传沉默相关的基因在高级别癌症中表达增强,而LMP肿瘤显示p53信号激活。LMP、低级别和高级别浆液性乳头状卵巢癌的表达谱表明,LMP肿瘤与高级别癌症不同;然而,它们与低级别癌症非常相似。p53通路成员的显著表达可能在LMP肿瘤表型中起重要作用。