Objectives: To examine whether loss of coxsackie and adenovirus receptor (CAR) expression is associated with bladder cancer characteristics and clinical outcomes and with expression of p53 and E-cadherin. Low levels of CAR are associated with decreased efficiency of adenovirus-mediated gene transduction of bladder transitional cell carcinoma.
Methods: Immunohistochemical staining for CAR and p53 was carried out on tissue microarrays from 62 patients who had undergone radical cystectomy. We also examined 30 specimens for E-cadherin expression.
Results: CAR expression was lost in 17 (27%) of 62 tumors. Loss of CAR expression was associated with metastases to regional lymph nodes (P = 0.049), muscle-invasive disease (P = 0.025), grade 3 disease (P = 0.038), altered p53 status (P = 0.041), and loss of E-cadherin expression (P = 0.042). With a median follow-up of 60 months, loss of CAR expression was associated with decreased bladder cancer-specific survival (P = 0.029) but not disease progression. When adjusted for the effects of standard pathologic features, only lymph node metastasis was associated with bladder transitional cell carcinoma progression and mortality.
Conclusions: Loss of CAR expression is associated with established markers of biologically aggressive bladder transitional cell carcinoma. The association of CAR with E-cadherin and p53 suggests a potential role for CAR in the regulation of urothelium integrity and the cell cycle.