Cyclooxygenase-2 expression in invasive transitional cell carcinoma of the urinary bladder

Abstract

Abstract. Cyclooxygenase-2 (COX-2) activity is reported to increase apoptosis, inhibit angiogenesis and reduce metastasis. We analyzed COX-2 expression in patients with invasive bladder cancer to evaluate the feasibility of selective COX-2 inhibitor treatment targeting COX-2. Forty patients with pathologically diagnosed invasive transitional cell carcinoma of the urinary bladder (pT2-pT4) were evaluated. Immunohistochemical staining was used to evaluate COX-2 expression, and cases with staining of ≥10% of tumor cells were defined as positive. In 2 patients, 0% of the primary tumors stained for COX-2, while 1-5% was stained in 16 patients, 5-10% in 3 patients and ≥10% in 19 patients (19/40, 47.5%). In terms of grade, 2 patients with grade 2 (2/3, 66.6%) and 17 patients with grade 3 (17/37, 45.4%) were COX-2 positive. When categorized by stage, 11 patients with pT2 (11/22, 50.0%), 6 with pT3 (6/13, 46.1%) and 2 with pT4 (2/5, 40.0%) were positive. Lymph node metastasis was observed in 10 patients; 2 of them, with pN2, were COX-2 positive. Those with COX-2-positive metastatic lymph nodes had grade 3 primary tumors, which were also COX-2 positive. In addition, COX-2-negative metastatic lymph node patients also had negative primary tumors. The results of this study suggest that 47.5% of patients with invasive bladder cancer may benefit from treatment with selective COX-2 inhibitors targeting COX-2, and that treatment efficacy can be expected in patients with lymph node metastasis when their primary tumors are COX-2 positive.

Cyclooxygenase-2 Expression in Urinary Bladder Transitional Cell Carcinoma and its Association with Clinicopathological Characteristics

“…This finding is consistent with some previous studies (Komhoff et al, 2000;Wulfing et al, 2004;Yamada et al, 2008;Naruse et al, 2010) and incompatible with the others (Matsuzawa et al, 2002;Shariat et al, 2003b;Wadhwa et al, 2005;Gurocak et al, 2006;Margulis et al, 2007;Jang and Lee, 2009). We also investigated whether there was any difference between muscle invasive tumors (≥P T2) and non -muscle invasive ones (Ta-T1) in the expression of COX-2, but we did not find any significant difference.…”

“…These contradictory results could be related to different causes such as limited number of cases or just selecting invasive bladder TCCs with grade 2 and 3 (Yamada et al, 2008;Naruse et al, 2010).…”

Increased COX-2 Immunostaining in Urothelial Carcinoma of the Urinary Bladder Is Associated with Invasiveness and Poor Prognosis

“…Similar previous findings were reported in previous studies [11, 32, 40]. But there are some other studies which failed to prove such association [29, 36]. Also, we reported that high COX-2 immunostaining is statistically associated with tumors with positive lymphovascular invasion similar to that of a previous report [36].…”

“…There are several studies reporting the same association [28, 32, 36]. On the other hand, other studies failed to show association between COX-2 expression and grade in UCB [20, 22, 24, 29, 37, 38].…”

“…COX-2 immunostaining was observed in areas of chronic cystitis, squamous metaplasia, and dysplasia [28]. On the other hand, others did not observe COX-2 expression in normal urothelial cells surrounding tumors [29]. This issue is very important and needs to be addressed on large-scale samples as it may be useful to use COX-2 inhibitors as chemopreventive for local tumor recurrence.…”