title: Tumor-associated stromal cells expressing E-prostanoid 2 or 3 receptors in prostate cancer: correlation with tumor aggressiveness and outcome by angiogenesis and lymphangiogenesis.
abstract: OBJECTIVE
  To clarify the detailed pathologic roles of prostaglandin E(2) in prostate cancer tissues, the present study investigated the clinical significance and prognostic roles of the density of tumor-associated stromal cells expressing specific receptors for prostaglandin E2, termed "E-prostanoid (EP)1-4 receptors (EP1R-4Rs)."
  
  
  METHODS
  The expression of each receptor was immunohistochemically examined in 114 formalin-fixed biopsy specimens. Correlations with clinicopathologic features were investigated in these specimens. Angiogenesis and lymphangiogenesis were measured by the percentage of CD34-stained vessels (microvessel density) and D2-40-stained vessels (lymph vessel density). The relationships between the density of each EPR-stained cells and the microvessel density or lymph vessel density were evaluated in 62 prostate cancer tissues obtained by radical surgery for more detailed analysis in a wider area of prostate cancer tissue.
  
  
  RESULTS
  The density of tumor-associated cells with EP2R expression was positively associated with the N (P<.001) and M (P=.002) stages. Similarly, EP3R-positive stromal cell density was significantly associated with the N (P=.033) and M (P=.026) stages. The density of EP2R- and EP3R-stained cells correlated with the microvessel density (r=0.42, P<.001) and lymph vessel density (r=0.36, P=.012), respectively. A greater density of EP2R-stained cells was recognized as an independent predictor of progression (hazard ratio 7.26, P=.002) on multivariate analysis.
  
  
  CONCLUSIONS
  EP2R- and EP3R-stained cells might play important roles in tumor progression, angiogenesis, and lymphangiogenesis in prostate cancer. The density of EP2R-stained stromal cells could offer a useful predictor of biochemical recurrence after radical surgery.
authors.affiliation: Department of Nephro-urology, Nagasaki University Graduate School of Biomedical Sciences, and Department of Pathology, Nagasaki University Hospital, Nagasaki, 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: Tomohiro
authors.initials: T
authors.lastname: Matsuo
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Watanabe
authors.forename: Tomayoshi
authors.initials: T
authors.lastname: Hayashi
authors.forename: Hideki
authors.initials: H
authors.lastname: Sakai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kanetake
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018450:Disease Progression; D006801:Humans; D053208:Kaplan-Meier Estimate; D042583:Lymphangiogenesis; D008297:Male; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D009367:Neoplasm Staging; D018919:Neovascularization, Physiologic; D016016:Proportional Hazards Models; D011467:Prostate / Q000166:cytology; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D058306:Receptors, Prostaglandin E, EP1 Subtype / Q000378:metabolism; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000378:metabolism*; D058308:Receptors, Prostaglandin E, EP3 Subtype / Q000378:metabolism*; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype