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.
Expression of the c-erbB-2 gene product and the epidermal growth factor receptor (EGF-R) was investigated in 54 cases of human bladder cancer immunohistologically and by Western blot analysis. For detection of the c-erbB-2 product, two specific antibodies, a rabbit polyclonal antibody directed to the intracellular domain and a murine monoclonal antibody recognizing an epitope in the extracellular domain, were used. Seventeen cases of bladder cancer were stained by the anti-c-erbB-2 polyclonal antibody, while 20 cases were stained by the monoclonal antibody, with good correlation on both stainings (p less than 0.01). There were four c-erbB-2 positive cases in 26 G1 tumors, four in 15 G2 tumors, and nine in 13 G3 tumors. There were also eight erbB-2 positive cases in nine muscle-invasive tumors, nine of 45 superficial tumors, four of five with lymph node metastasis, and seven of 14 without metastasis, as revealed by staining with the polyclonal antibody. Thus, the c-erbB-2 gene product was more frequently expressed in high grade tumors (p less than 0.01), in high stage tumors (p less than 0.01), and nodal metastatic tumors (N.S. by Chi-square test). Twenty-two of the 54 tumors were stained by an anti-EGF-R monoclonal antibody, 528 IgG. The expression of EGF-R was independent of histological grading, tumor stage, and nodal status, and no correlation was observed between expression of the c-erbB-2 product and EGF-R. The c-erbB-2 product may be applicable as a tumor marker for evaluation of malignant potential, invasiveness, and probably metastatic potential of human bladder cancer.
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