Loss of coxsackie and adenovirus receptor expression is associated with features of aggressive bladder cancer

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..