This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, E. Articles by Marincola, F. M. Search for Related Content PubMed PubMed Citation Articles by Wang, E. Articles by Marincola, F. M.

Peritoneal and Subperitoneal Stroma May Facilitate Regional Spread of Ovarian Cancer

¹ Immunogenetics Section, Department of Transfusion Medicine, NIH, Bethesda, Maryland and Departments of ² Gynecologic Oncology, ³ Pathology, ⁴ Biostatistics, ⁵ Surgical Oncology, and ⁶ Molecular Pathology, the University of Texas M.D. Anderson Cancer Center, Houston, Texas

Requests for reprints: Francesco M. Marincola, Immunogenetics Section, Department of Transfusion Medicine, Clinical Center, Building 10, R-1C711, NIH, Bethesda, MD 20892. Phone: 301-451-4967; Fax: 301-402-1360; E-mail: FMarincola{at}cc.nih.gov.

Purpose: 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.

Experimental Design: 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 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.

This article has been cited by other articles:

				C. N. Landen Jr, M. J. Birrer, and A. K. Sood Early Events in the Pathogenesis of Epithelial Ovarian Cancer J. Clin. Oncol., February 20, 2008; 26(6): 995 - 1005. [Abstract] [Full Text] [PDF]

				R. S. Freedman, E. Wang, S. Voiculescu, R. Patenia, R. L. Bassett Jr., M. Deavers, F. M. Marincola, P. Yang, and R. A. Newman Comparative Analysis of Peritoneum and Tumor Eicosanoids and Pathways in Advanced Ovarian Cancer Clin. Cancer Res., October 1, 2007; 13(19): 5736 - 5744. [Abstract] [Full Text] [PDF]

				T. M. Robinson-Smith, I. Isaacsohn, C. A. Mercer, M. Zhou, N. Van Rooijen, N. Husseinzadeh, M. M. McFarland-Mancini, and A. F. Drew Macrophages Mediate Inflammation-Enhanced Metastasis of Ovarian Tumors in Mice Cancer Res., June 15, 2007; 67(12): 5708 - 5716. [Abstract] [Full Text] [PDF]

				C. F. Basil, Y. Zhao, K. Zavaglia, P. Jin, M. C. Panelli, S. Voiculescu, S. Mandruzzato, H. M. Lee, B. Seliger, R. S. Freedman, et al. Common cancer biomarkers. Cancer Res., March 15, 2006; 66(6): 2953 - 2961. [Abstract] [Full Text] [PDF]

				I. O. Gordon and R. S. Freedman Defective Antitumor Function of Monocyte-Derived Macrophages from Epithelial Ovarian Cancer Patients Clin. Cancer Res., March 1, 2006; 12(5): 1515 - 1524. [Abstract] [Full Text] [PDF]