Expression profiling of mucinous tumors of the ovary identifies genes of clinicopathologic importance.
OBJECTIVE
To elucidate the molecular mechanisms contributing to the unique clinicopathologic characteristics of mucinous ovarian carcinoma, global gene expression profiling of mucinous ovarian tumors was carried out.


METHODS
Gene expression profiling was completed for 25 microdissected mucinous tumors [6 cystadenomas, 10 low malignant potential (LMP) tumors, and 9 adenocarcinomas] using Affymetrix U133 Plus 2.0 oligonucleotide microarrays. Hierarchical clustering and binary tree prediction analysis were used to determine the relationships among mucinous specimens and a series of previously profiled microdissected serous tumors and normal ovarian surface epithelium. PathwayAssist software was used to identify putative signaling pathways involved in the development of mucinous LMP tumors and adenocarcinomas.


RESULTS
Comparison of the gene profiles between mucinous tumors and normal ovarian epithelial cells identified 1,599, 2,916, and 1,765 differentially expressed in genes in the cystadenomas, LMP tumors, and adenocarcinomas, respectively. Hierarchical clustering showed that mucinous and serous LMP tumors are distinct. In addition, there was a close association of mucinous LMP tumors and adenocarcinomas with serous adenocarcinomas. Binary tree prediction revealed increased heterogeneity among mucinous tumors compared with their serous counterparts. Furthermore, the cystadenomas coexpressed a subset of genes that were differentially regulated in LMP and adenocarcinoma specimens compared with normal ovarian surface epithelium. PathwayAssist highlighted pathways with expression of genes involved in drug resistance in both LMP and adenocarcinoma samples. In addition, genes involved in cytoskeletal regulation were specifically up-regulated in the mucinous adenocarcinomas.


CONCLUSIONS
These data provide a useful basis for understanding the molecular events leading to the development and progression of mucinous ovarian cancer.
Wamunyokoli
Fred W
FW
Cell and Cancer Biology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
Bonome
Tomas
T
Lee
Ji-Young
JY
Feltmate
Colleen M
CM
Welch
William R
WR
Radonovich
Mike
M
Pise-Masison
Cindy
C
Brady
John
J
Hao
Ke
K
Berkowitz
Ross S
RS
Mok
Samuel
S
Birrer
Michael J
MJ
D002288:Adenocarcinoma, Mucinous / Q000145:classification / Q000235:genetics* / Q000473:pathology*; D016000:Cluster Analysis; D003663:Decision Trees; D003937:Diagnosis, Differential; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010051:Ovarian Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology*; D011237:Predictive Value of Tests