Patterns of gene expression in different histotypes of epithelial ovarian cancer correlate with those in normal fallopian tube, endometrium, and colon.
OBJECTIVE
Epithelial ovarian cancers are thought to arise from flattened epithelial cells that cover the ovarian surface or that line inclusion cysts. During malignant transformation, different histotypes arise that resemble epithelial cells from normal fallopian tube, endometrium, and intestine. This study compares gene expression in serous, endometrioid, clear cell, and mucinous ovarian cancers with that in the normal tissues that they resemble.


METHODS
Expression of 63,000 probe sets was measured in 50 ovarian cancers, in 5 pools of normal ovarian epithelial brushings, and in mucosal scrapings from 4 normal fallopian tube, 5 endometrium, and 4 colon specimens. Using rank-sum analysis, genes whose expressions best differentiated the ovarian cancer histotypes and normal ovarian epithelium were used to determine whether a correlation based on gene expression existed between ovarian cancer histotypes and the normal tissues they resemble.


RESULTS
When compared with normal ovarian epithelial brushings, alterations in serous tumors correlated with those in normal fallopian tube (P = 0.0042) but not in other normal tissues. Similarly, mucinous cancers correlated with those in normal colonic mucosa (P = 0.0003), and both endometrioid and clear cell histotypes correlated with changes in normal endometrium (P = 0.0172 and 0.0002, respectively). Mucinous cancers displayed the greatest number of alterations in gene expression when compared with normal ovarian epithelial cells.


CONCLUSIONS
Studies at a molecular level show distinct expression profiles of different histologies of ovarian cancer and support the long-held belief that histotypes of ovarian cancers come to resemble normal fallopian tube, endometrial, and colonic epithelium. Several potential molecular markers for mucinous ovarian cancers have been identified.
Marquez
Rebecca T
RT
Department of Experimental Therapeutics, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. rtmarquez@mdanderson.org
Baggerly
Keith A
KA
Patterson
Andrea P
AP
Liu
Jinsong
J
Broaddus
Russell
R
Frumovitz
Michael
M
Atkinson
Edward N
EN
Smith
David I
DI
Hartmann
Lynn
L
Fishman
David
D
Berchuck
Andrew
A
Whitaker
Regina
R
Gershenson
David M
DM
Mills
Gordon B
GB
Bast
Robert C
RC
Lu
Karen H
KH
D018262:Adenocarcinoma, Clear Cell / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D018269:Carcinoma, Endometrioid / Q000235:genetics / Q000378:metabolism; D003106:Colon / Q000378:metabolism*; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism; D018291:Cystadenoma, Mucinous / Q000235:genetics / Q000378:metabolism; D004717:Endometrium / Q000378:metabolism*; D005187:Fallopian Tubes / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; D012333:RNA, Messenger