Cyclooxygenase-2 is Highly Expressed in Carcinoma in Situ and T1 Transitional Cell Carcinoma of the Bladder

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Abstract
We describe cyclooxygenase-2 (COX-2) expression patterns in patients with carcinoma in situ and/or stage T1 transitional cell carcinoma. We determined whether expression is associated with clinical outcome in these patients. Immunostaining for COX-2 was performed on paraffin embedded bladder biopsy specimens from 2 independent groups of patients without muscle invasive carcinoma, including 39 with carcinoma in situ and 34 with stage T1 tumors. Immunoreactivity was scored as the percent of carcinoma in situ cells with cytoplasmic staining for COX-2 in the carcinoma in situ group and as the percent of stage T1 cells expressing COX-2 in the stage T1 transitional cell carcinoma group. We evaluated other molecular alterations, including E-cadherin, p21 and p53, because evidence suggests a biological association of COX-2 with alterations in these molecular markers. In the carcinoma in situ group 5 patients (13%) had no immunoreactivity, while 2 (5%), 5 (13%) and 27 (69%) had 10%, 20% and 30% or greater carcinoma in situ cells positive for COX-2, respectively. In the transitional cell carcinoma group 1 (3%), 4 (12%) and 29 (85%) patients had 10%, 20% and 30% or greater positive cells, respectively. COX-2 expression was not associated with any clinical or pathological parameters, or with molecular markers regardless of the cutoff used. It was also not associated with clinical outcomes in the stage T1 transitional cell carcinoma group. In the carcinoma in situ group COX-2 expression was significantly associated with disease recurrence using cutoffs of 0% and greater than 10% positive cells, and with disease progression using a greater than 20% cutoff. However, it was not associated with bladder cancer related survival. COX-2 is expressed in a high percent of patients with carcinoma in situ and stage T1 transitional cell carcinoma, supporting the rationale for chemoprevention studies with selective COX-2. We could not substantiate a role for COX-2 immunohistochemistry for the staging and prognosis of carcinoma in situ and/or stage T1 transitional cell carcinoma.