A histopathologic investigation of PGE2 pathways as predictors of proliferation and invasion in urothelial carcinomas of the bladder Journal Article


Authors: Eschwège, P.; Ferlicot, S.; Droupy, S.; Ba, N.; Conti, M.; Loric, S.; Coindard, G.; Denis, I.; Ferretti, L.; Cornelius, A.; Legrand, A.; Bedossa, P.; Benoît, G.; Jardin, A.; Scardino, P.
Article Title: A histopathologic investigation of PGE2 pathways as predictors of proliferation and invasion in urothelial carcinomas of the bladder
Abstract: Introduction and Objectives: The pattern of arachidonate acid (AA) transformation in tumor cells has been shown to play a role in determining tumor cell invasiveness. AA is released from membrane phospholipids by cPLA 2. Then it is metabolized into prostaglandins and PGE2 especially via cyclooxygenase pathways. PGE2 production seems to be necessary for rendering the cells invasive. We aimed to characterize cPLA 2, cyclooxygenase 2 (COX2) and prostaglandine E synthase (PGES) expression in human transitional carcinoma (TCC) of the urinary bladder and correlate with the Ki-67 proliferating marker. Methods: Formalin-fixed human TCC tissues (n = 54) obtained from TURB or cystectomies were evaluated for cPLA2, COX2, PGES and Ki-67 expression using specific antibodies. There were 6 CIS, 9 pTaG1, 9 pTaG3, 10 pT1G3 and 10 pT2G3. 10 normal bladder tissues were also evaluated. Control slides were incubated without primary antibodies and treated in a similar way. Results: cPLA2, COX2 and PGES were not expressed in the 10 normal tissues. In the same normal tissues, Ki-67 expression was observed only in 1% of the cells. However, cPLA 2 was expressed in 1/6 CIS, 1/9 pTaG1, 3/9 pTaG3, 6/10 pT1G3 and 2/10 pT2G3. COX2 was expressed in 0/6 CIS, 0/10 pTaG1, 2/9 pTaG3, 3/ 10 pT1G3 and 1/10 pT2G3. PGES was expressed in 4/6 CIS, 0/9 pTaG1, 4/9 pTaG3, 2/10 pT1G3 and 5/10 pT2G3. Ki-67 expression was 39.5% for CIS, 6.5% in pTaG1, 37% in pTaG3, 34.5% in pT1G3 and 55% in pT2G3. If we consider it a positive result when at least one enzyme was expressed, there were 5/6 CIS positive, 1/9 pTaG1 positive, 9/9 pTaG3 positive, 10/10 pT1G3 positive and 10/10 pT2G3 positive. Also the Ki-67 is more often expressed in cells with high grade tumor. Conclusions: These results suggest that (i) not only COX2 is involved in the tumorogenesis of the TCC but also cPLA2 and PGES, (ii) there is relationship between the AA metabolic PGE2 pathway expression and the aggressiveness of the TCC of the urinary bladder. © 2003 Elsevier B.V. All rights reserved.
Keywords: immunohistochemistry; signal transduction; adult; clinical article; controlled study; human tissue; protein expression; aged; aged, 80 and over; middle aged; histopathology; protein localization; ki 67 antigen; cell proliferation; cell division; molecular dynamics; prediction; urinary bladder neoplasms; carcinogenesis; cancer invasion; molecular mechanics; correlation analysis; ki-67; cyclooxygenase 2; prostaglandins; prostaglandin e2; cystectomy; urinary bladder; urothelial carcinoma; predictive value of tests; antibody specificity; neoplasm invasiveness; proliferation; carcinoma, transitional cell; bladder carcinoma; arachidonic acid; phospholipase a2; transitional cell carcinoma; dinoprostone; prostaglandin synthase; cytosolic phospholipase a2; humans; human; male; female; priority journal; article; prostaglandin e synthase
Journal Title: European Urology
Volume: 44
Issue: 4
ISSN: 0302-2838
Publisher: Elsevier Science, Inc.  
Date Published: 2003-10-01
Start Page: 435
End Page: 441
Language: English
DOI: 10.1016/s0302-2838(03)00313-0
PUBMED: 14499677
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 12 September 2014 -- Source: Scopus
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  1. Peter T Scardino
    671 Scardino