Prognostic Values of p53 and HER-2/neu Coexpression in Invasive Bladder Cancer in Taiwan

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Abstract
Objectives: To explore the clinical significance of p53 and HER-2/neu coexpression by immunohistochemistry in patients with invasive bladder cancer in Taiwan. Methods: Paraffin-embedded tumor blocks were obtained from 67 patients with invasive bladder cancer subjected to radical cystectomy, bilateral lymph node dissection, and urinary diversion with or without systemic chemotherapy. Two observers (N.H.C. and T.S.T.), blinded to clinical outcome, reviewed the immunohistochemical staining for p53 (PAb1801) and HER-2/neu (Ab-17). The results were analyzed for progression-free survival and patient survival. Results: Positive staining for p53 and HER-2/neu was found in 30 (44.8%) and 39 (58.2%) patients. In contrast to HER-2/neu, p53 expression was significantly associated with tumor grade and pathologic stage (p = 0.040 and 0.004, respectively), and tended to be related to the nodal status (p = 0.080). Most importantly, coexpression of p53 and HER-2/neu significantly correlated with nodal metastases (p = 0.020). Univariate and multivariate analysis revealed p53 and nodal status as two independent prognostic factors. Additionally, patients with p53 and HER-2/neu coexpression had the shortest time to relapse and overall survival, irrespective of whether adjuvant chemotherapy was given or not (p = 0.005 and 0.030). Conclusions: In invasive bladder cancer, p53 was an important prognostic factor since its expression correlated with tumor grade and stage, even nodal status, whereas HER-2/neu did not show prognostic significance. Tumors with p53 and HER-2/neu coexpression were associated with nodal metastases, probably resulting in decreased progression-free survival. Although some basic studies provide some important supports, studies including larger patient cohorts would still be required to prove the hypothesis that p53 and HER-2/neu-coexpressing tumors have a worse prognosis and are more resistant to a cisplatin-based multidrug regimen.

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