An immunohistologic evaluation of C-erbB-2 gene product in patients with urinary bladder carcinoma

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Abstract
Background. Amplification or overexpression of the c‐erbB‐2 gene have been reported to correlate with poor patient prognosis in human breast, gastric, and ovarian cancer. Recently, the c‐erbB‐2 gene product was found to be expressed frequently in the urinary bladder carcinoma. In the current study, the presence of the c‐erbB‐2 gene product in urinary bladder carcinomas was compared with patient outcome to evaluate whether c‐erbB‐2 gene product could identify a subset of patients who are destined to have a poor prognosis. Methods. Immunohistologic study of the c‐erbB‐2 gene product was done in formaldehyde‐fixed paraffin‐embedded tissue specimens obtained from 88 transitional cell carcinomas of the human urinary bladder. Eighty‐three patients who underwent complete tumor resection by total cystoprostatectomy (30 patients) or by bladder‐preserving operations such as transurethral surgery (50 patients) or partial cystectomy (3 patients) entered a follow‐up study. The other five patients did not enter the follow‐up study because of lost follow‐up (2 patients) or distant metastasis at the time of surgery. Results. The c‐erbB‐2 gene product was expressed in 23 of 88 patients (26%), showing an increase in the expression rate corresponding to the advancement of tumor grade (P < 0.05) and tumor stage (P < 0.2). The 5‐year disease‐free survival rate was 48.5% for patients with c‐erbB‐2 negative tumors versus 9.7% for those with c‐erbB‐2 positive tumors (P < 0.01). The 5‐year actuarial survival rate was 65.5% for patients with c‐erbB‐2 negative tumors versus 41.8% for those with c‐erbB‐2 positive tumors (P < 0.05). Multivariate analysis using Cox regression model showed that the c‐erbB‐2 gene product tissue status was a significant prognostic factor independent of grade and stage of the tumor. Conclusions. The results suggest that the c‐erbB‐2 gene product could be a tumor marker to identify a malignant subgroup in bladder carcinomas. Cancer 1992; 70:2493‐2498.