title: Pathological function of prostaglandin E2 receptors in transitional cell carcinoma of the upper urinary tract.
abstract: The prostaglandin E2 receptor, EP4 receptor (EP4R), plays an important role in the development of transitional cell carcinoma of the upper urinary tract (TCC-UUT). However, the clinical significance of other EP receptors (EP1R-3R) is not clear. Furthermore, the pathological function of EP receptors in such patients is not understood. In the present study, we examined the expression of EP1R-3R in 101 TCC-UUT tissues by immunohistochemistry. Furthermore, we defined the relationship between cyclooxygenase (COX)-2 and EP receptor expression, proliferation index (PI), microvessel density (MVD), and expression of metalloproteinase-2 (MMP-2), urokinase-type plasminogen activator (uPA), and exon v6 containing CD44 isoform (CD44 v6) by multivariate analysis. The expression of EP1R, EP2R, and EP3R was positive in 20 (19.8%), 26 (25.7%), and 14 (13.9%) tumor samples, respectively. Expression of these receptors was not associated with pathological findings or survival. COX-2 and EP4R were independently associated with MVD and MMP-2, and uPA or PI and MMP-2, respectively. Other EP receptors were not influenced by any factors. Our results suggest that EP1R-3R play a minimal role in cancer progression in patients with TCC-UUT. On the other hand, EP4R regulates tumor progression via cancer cell proliferation and MMP-2, distinct from COX-2.
authors.affiliation: Department of Urology, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. int.doc.miya@m3.dion.ne.jp
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Miyata
authors.forename: Kojiro
authors.initials: K
authors.lastname: Ohba
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kanda
authors.forename: Koichiro
authors.initials: K
authors.lastname: Nomata
authors.forename: Jiro
authors.initials: J
authors.lastname: Eguchi
authors.forename: Tomayoshi
authors.initials: T
authors.lastname: Hayashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kanetake
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D002295:Carcinoma, Transitional Cell / Q000098:blood supply / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007124:Immunoenzyme Techniques; D007680:Kidney Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D007682:Kidney Pelvis / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008833:Microcirculation / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D018078:Receptors, Prostaglandin E / Q000378:metabolism*; D015996:Survival Rate; D014516:Ureteral Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000401:mortality / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D018078:Receptors, Prostaglandin E; D051546:Cyclooxygenase 2