This Article Full Text Full Text (PDF) Supplementary Data 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 Davidson, B. Articles by Shih, I.-M. Search for Related Content PubMed PubMed Citation Articles by Davidson, B. Articles by Shih, I.-M.

Gene Expression Signatures Differentiate Ovarian/Peritoneal Serous Carcinoma from Diffuse Malignant Peritoneal Mesothelioma

Authors' Affiliations: ¹ Department of Pathology, Radiumhospitalet-Rikshospitalet Medical Center, University of Oslo, Oslo, Norway; and Departments of ² Pathology and ³ Gynecology and Oncology, Johns Hopkins Medical Institutions, Baltimore Maryland

Requests for reprints: Ben Davidson, Department of Pathology, Radiumhospitalet-Rikshospitalet Medical Center, Montebello N-0310 Oslo, Norway. Phone: 47-22934871; Fax: 47-22508554; E-mail: ben.davidson{at}radiumhospitalet.no.

Purpose: Ovarian/primary peritoneal serous carcinoma (OC/PPC) and diffuse peritoneal malignant mesothelioma (DMPM) are highly aggressive tumors that are closely related morphologically and histogenetically. It remains unclear whether both tumors are molecularly distinct neoplasms. The current study compared global gene expression patterns in OC/PPC and DMPM.

Experimental Design: Ten OC/PPC and five DMPM effusions were analyzed for gene expression profiles using the Affymetrix U133 Plus 2 arrays and the dCHIP analysis program. Differentially expressed candidate genes were validated using quantitative real-time PCR and immunohistochemistry.

Results: Unsupervised hierarchical clustering using all 54,675 genes in the array classified the samples into two groups: DMPM specimens versus OC/PPC specimens. A total of 189 genes that were differentially expressed in these two groups were selected based on statistical significance. Genes overexpressed in DMPM (n = 68) included calretinin, vitronectin, claudin 15, ₄ laminin, hyaluronan synthase 1, cadherin 11, RAB7, v-maf, and the epidermal growth factor–containing fibulin-like extracellular matrix protein 1. Genes overexpressed in OC/PPC (n = 121) included insulin-like growth factor II (IGF-II); IGF-II binding protein 3; cyclin E1; folate receptors 1 and 3; RAB25; MUC4; endothelin-1; CD24; kallikreins 6, 7, and 8; claudins 3, 4, and 6; Notch3; and MMP-7. Quantitative real-time PCR validated the differential expression of 13 genes, and immunohistochemistry confirmed the differences for four gene products.

Conclusions: Expression profiling separates OC/PPC from DMPM and identifies a number of genes that are differentially expressed in these tumors. The molecular signatures unique to OC/PPC and DMPM should provide a molecular basis to study both tumors and new potential markers for facilitating their differential diagnosis.

This article has been cited by other articles:

				O. Rayhman, E. Klipper, L. Muller, B. Davidson, R. Reich, and R. Meidan Small Interfering RNA Molecules Targeting Endothelin-Converting Enzyme-1 Inhibit Endothelin-1 Synthesis and the Invasive Phenotype of Ovarian Carcinoma Cells Cancer Res., November 15, 2008; 68(22): 9265 - 9273. [Abstract] [Full Text] [PDF]

				M. A. Gates, S. S. Tworoger, K. L. Terry, L. Titus-Ernstoff, B. Rosner, I. De Vivo, D. W. Cramer, and S. E. Hankinson Talc Use, Variants of the GSTM1, GSTT1, and NAT2 Genes, and Risk of Epithelial Ovarian Cancer Cancer Epidemiol. Biomarkers Prev., September 1, 2008; 17(9): 2436 - 2444. [Abstract] [Full Text] [PDF]