Peritoneal and subperitoneal stroma may facilitate regional spread of ovarian cancer.
OBJECTIVE
Epithelial ovarian cancer (EOC) is characterized by early peritoneal involvement ultimately contributing to morbidity and mortality. To study the role of the peritoneum in fostering tumor invasion, we analyzed differences between the transcriptional repertoires of peritoneal tissue lacking detectable cancer in patients with EOC versus benign gynecologic disease.


METHODS
Specimens were collected at laparotomy from patients with benign disease (b) or malignant (m) ovarian pathology and comprised primary ovarian tumors, paired bilateral specimens from adjacent peritoneum and attached stroma (PE), subjacent stroma (ST), peritoneal washes, ascites, and peripheral blood mononuclear cells. Specimens were immediately frozen. RNA was amplified by in vitro transcription and cohybridized with reference RNA to a custom-made 17.5k cDNA microarray.


RESULTS
Principal component analysis and unsupervised clustering did not segregate specimens from patients with benign or malignant pathology. Class comparison identified differences between benign and malignant PE and ST specimens deemed significant by permutation test (P = 0.027 and 0.012, respectively). A two-tailed Student's t test identified 402 (bPE versus mPE) and 663 (mST versus bST) genes differentially expressed at a significance level of P2 < or = 0.005 when all available paired samples from each patient were analyzed. The same comparison using one sample per patient reduced the pool of differentially expressed genes but retained permutation test significance for bST versus mST (P = 0.031) and borderline significance for bPE versus mPE (P = 0.056) differences.


CONCLUSIONS
The presence of EOC may foster peritoneal implantation and growth of cancer cells by inducing factors that may represent molecular targets for disease control.
Wang
Ena
E
Immunogenetics Section, Department of Transfusion Medicine, NIH, Bethesda, Maryland 20892, USA.
Ngalame
Yvonne
Y
Panelli
Monica C
MC
Nguyen-Jackson
Hoainam
H
Deavers
Michael
M
Mueller
Peter
P
Hu
Wei
W
Savary
Cherylyn A
CA
Kobayashi
Ryuji
R
Freedman
Ralph S
RS
Marincola
Francesco M
FM
D019295:Computational Biology; D018076:DNA, Complementary / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000473:pathology*; D010053:Ovary / Q000473:pathology; D010537:Peritoneum / Q000473:pathology; D012313:RNA / Q000378:metabolism; D017154:Stromal Cells / Q000473:pathology*; D014158:Transcription, Genetic; D015854:Up-Regulation
D018076:DNA, Complementary; D012313:RNA