Gene expression in ovarian cancer reflects both morphology and biological behavior, distinguishing clear cell from other poor-prognosis ovarian carcinomas.
Biologically and clinically meaningful tumor classification schemes have long been sought. Some malignant epithelial neoplasms, such as those in the thyroid and endometrium, exhibit more than one pattern of differentiation, each associated with distinctive clinical features and treatments. In other tissues, all carcinomas, regardless of morphological type, are treated as though they represent a single disease. To better understand the biological and clinical features seen in the four major histological types of ovarian carcinoma (OvCa), we analyzed gene expression in 113 ovarian epithelial tumors using oligonucleotide microarrays. Global views of the variation in gene expression were obtained using PCA. These analyses show that mucinous and clear cell OvCas can be readily distinguished from serous OvCas based on their gene expression profiles, regardless of tumor stage and grade. In contrast, endometrioid adenocarcinomas show significant overlap with other histological types. Although high-stage/grade tumors are generally separable from low-stage/grade tumors, clear cell OvCa has a molecular signature that distinguishes it from other poor-prognosis OvCas. Indeed, 73 genes, expressed 2- to 29-fold higher in clear cell OvCas compared with each of the other OvCa types, were identified. Collectively, the data indicate that gene expression patterns in ovarian adenocarcinomas reflect both morphological features and biological behavior. Moreover, these studies provide a foundation for the development of new type-specific diagnostic strategies and treatments for ovarian cancer.
Departments of Pathology, The University of Michigan, Ann Arbor, Michigan. 48109, USA.
Donald R
DR
Schwartz
Sharon L R
SL
Kardia
Kerby A
KA
Shedden
Rork
R
Kuick
George
G
Michailidis
Jeremy M G
JM
Taylor
David E
DE
Misek
Rong
R
Wu
Yali
Y
Zhai
Danielle M
DM
Darrah
Heather
H
Reed
Lora H
LH
Ellenson
Thomas J
TJ
Giordano
Eric R
ER
Fearon
Samir M
SM
Hanash
Kathleen R
KR
Cho
D018262:Adenocarcinoma, Clear Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D015203:Reproducibility of Results