A histopathologic investigation of PGE(2) pathways as predictors of proliferation and invasion in urothelial carcinomas of the bladder.
OBJECTIVE
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 PGE(2) especially via cyclooxygenase pathways. PGE(2) 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 cPLA(2), 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
cPLA(2), 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 cPLA(2) and PGES, (ii). there is relationship between the AA metabolic PGE(2) pathway expression and the aggressiveness of the TCC of the urinary bladder.
D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000201:enzymology* / Q000473:pathology*; D002455:Cell Division; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011237:Predictive Value of Tests; D001749:Urinary Bladder Neoplasms / Q000201:enzymology* / Q000473:pathology*
D015232:Dinoprostone