title: Cyclooxygenase-2 expression in endometrial cancer: correlation with microvessel count and expression of vascular endothelial growth factor and thymidine phosphorylase.
abstract: Cyclooxygenase-2 (COX-2), known to be elevated in several human cancers, regulates angiogenesis by inducing production of angiogenic factors. These mechanisms require clarification in endometrial cancer. COX-2 expression was examined by immunohistochemistry and reverse-transcription polymerase chain reaction (RT-PCR) in endometrial cancer, endometrial hyperplasia, and normal endometrium in various phases. We investigated the relationship between COX-2 expression and clinicopathologic variables, microvessel count, and expression of vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP). Immunohistochemistry demonstrated COX-2 protein in cancerous epithelial cells but not in stromal cells. COX-2 expression in epithelial cells was significantly greater in endometrial cancer (n = 63) and endometrial hyperplasia (n = 6) than in normal endometrium in any phase (n = 53). Although COX-2 did not correlate with any conventional clinicopathologic factor in patients with endometrial cancer, COX-2 expression was associated with high microvessel count, VEGF expression, and TP expression. By combined analysis of COX-2, VEGF, and TP, tumors with high expression of at least one factor had a significantly higher microvessel count than tumors expressing little of the three factors. We confirmed upregulation of COX-2 mRNA expression by RT-PCR in endometrial cancer (n = 17) compared to normal endometrium (n = 12). COX-2 mRNA expression significantly correlated with VEGF mRNA expression in these tumors. COX-2 is upregulated in endometrial cancer and facilitates tumor growth via angiogenesis produced in associated with VEGF and TP. Specific inhibition of COX-2 may be a useful therapeutic intervention in endometrial cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Shimane Medical University, Izumo, Japan.
authors.forename: Ritsuto
authors.initials: R
authors.lastname: Fujiwaki
authors.forename: Kohji
authors.initials: K
authors.lastname: Iida
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Kanasaki
authors.forename: Tomoya
authors.initials: T
authors.lastname: Ozaki
authors.forename: Kohkichi
authors.initials: K
authors.lastname: Hata
authors.forename: Kohji
authors.initials: K
authors.lastname: Miyazaki
mesh_terms: D051546:Cyclooxygenase 2; D004714:Endometrial Hyperplasia / Q000201:enzymology; D016889:Endometrial Neoplasms / Q000201:enzymology* / Q000473:pathology*; D004717:Endometrium / Q000201:enzymology; D016228:Endothelial Growth Factors / Q000032:analysis / Q000235:genetics*; D004847:Epithelial Cells / Q000201:enzymology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis / Q000235:genetics*; D008222:Lymphokines / Q000032:analysis / Q000235:genetics*; D008565:Membrane Proteins; D008833:Microcirculation / Q000473:pathology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000201:enzymology; D013939:Thymidine Phosphorylase / Q000032:analysis / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D007527:Isoenzymes; D008222:Lymphokines; D008565:Membrane Proteins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D013939:Thymidine Phosphorylase