Expression of cyclooxygenase-2 in human transitional cell carcinoma of the urinary bladder

Abstract

Recent studies suggest that expression of cyclooxygenase-2 (Cox-2) is elevated in transitional cell carcinoma (TCC) of the urinary bladder and that inhibition of Cox-2 activity suppresses bladder cancer in experimental animal models. We have investigated the expression of Cox-2 protein in human TCCs (n = 85), in in situ carcinomas (Tis) of the urinary bladder (n = 17), and in nonneoplastic urinary bladder samples (n = 16) using immunohistochemistry. Cox-2 immunoreactivity was detected in 66% (67 of 102) of the carcinomas, whereas only 25% (4 of 16) of the nonneoplastic samples were positive (P: < 0.005). Cox-2 immunoreactivity localized to neoplastic cells in the carcinoma samples. The rate of positivity was the same in invasive (T1-3; 70%, n = 40) and in noninvasive (Tis and Ta; 65%, n = 62) carcinomas, but noninvasive tumors had a higher frequency (32%) of homogenous pattern of staining (>90% of the tumor cells positive) than the invasive carcinomas (10%) (P: < 0.05). However, several invasive TCCs exhibited the strongest intensity of Cox-2 staining in the invading cells, whereas other parts of the tumor were virtually negative. Finally, strong Cox-2 positivity was also found in nonneoplastic ulcerations (2 of 2) and in inflammatory pseudotumors (2 of 2), in which the immunoreactivity localized to the nonepithelial cells. Taken together, our data suggest that Cox-2 is highly expressed in noninvasive bladder carcinomas, whereas the highest expression of invasive tumors associated with the invading cells, and that Cox-2 may also have a pathophysiological role in nonneoplastic conditions of the urinary bladder, such as ulcerations and inflammatory pseudotumors.

Figure 1.

Immunohistochemical detection of Cox-2 protein in the human urinary bladder specimens using a Cox-2-specific monoclonal antibody. A: Normal transitional cell epithelium was negative or stained with weak intensity (B, pre-adsorption control using an antigenic peptide). C to L: Cox-2 immunoreactivity localized to the neoplastic cells in the TCC specimens, but tumor stroma remained negative. C: In situ carcinoma (D, the pre-adsorption control). E: Noninvasive (Ta) carcinoma (F, the pre-adsorption control). G: Invasive (T1) carcinoma (H, the pre-adsorption control). I: Invading cells of a T3 carcinoma (J, the pre-adsorption control). K and L: Cox-2 positivity in an invasive (T3) carcinoma, whereas normal transitional cell epithelial cells (asterisks) remained essentially negative. M to P: Strong Cox-2 positivity at sites of nonneoplastic ulcerations and in inflammatory pseudotumors, in which the immunoreactivity localized to the nonepithelial cells. M: Ulceration (N, the pre-adsorption control). O: Inflammatory pseudotumor (P, the pre-adsorption control). Original magnifications: ×600 (A–J and L–P ) and ×200 (K).