Correlation of cyclooxygenase-2 expression with molecular markers, pathological features and clinical outcome of transitional cell carcinoma of the bladder.
OBJECTIVE
We investigated the relationship between cyclooxygenase-2 (COX-2) expression and molecular alterations commonly found in transitional cell carcinoma (TCC) of the bladder and determined whether COX-2 immunoreactivity is associated with cancer stage, progression and survival in patients undergoing radical cystectomy.


METHODS
Immunohistochemical staining for COX-2 was done in archival tumor specimens from 80 patients who underwent radical cystectomy. Immunoreactivity was categorized as positive (reactivity in greater than 10% tumor cells) or negative. Microvessel density, E-cadherin, pRB, p16, p21, p53 and transforming growth factor (TGF)-beta1 and its receptors (types I and II) were also studied because evidence suggests a biological association between COX-2 and alteration of these molecules.


RESULTS
COX-2 was over expressed in 62 patients (78%). COX-2 over expression was associated with muscle invasive pathological stage (p = 0.022), TGF-beta1 over expression (p = 0.004), decreased E-cadherin expression (p < 0.001), and altered expression of pRB (p = 0.003) and p16 (p = 0.006). At a median followup of 101 months COX-2 over expression was associated with disease progression (p = 0.038) and bladder cancer specific survival (p = 0.042). However, when adjusted for the effects of standard pathological features, only lymph node metastasis was associated with bladder cancer progression (p = 0.027) and mortality (p = 0.042).


CONCLUSIONS
COX-2 is commonly expressed in patients with bladder TCC. Using the cutoff of 10% abnormal COX-2 expression is associated with the degree of invasiveness, alterations in TGF-beta1 and pRB/p16 pathways, and loss of cell adhesion. While COX-2 expression has limited prognostic value in patients with bladder TCC, it may serve as a target for therapy with selective COX-2 inhibitors.
Shariat
Shanrokh F
SF
Scott Department of Urology, Baylor College of Medicine, 6560 Fannin, Houston, TX 77030, USA.
Matsumoto
Kazumasa
K
Kim
JaHong
J
Ayala
Gustavo E
GE
Zhou
Jain-Hua
JH
Jian
Weiguo
W
Benedict
William F
WF
Lerner
Seth  P
S
D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D051546:Cyclooxygenase 2; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins; D015999:Multivariate Analysis; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology
D015820:Cadherins; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases