p53 but not erbB-2 expression is associated with rapid tumor proliferation in urinary bladder cancer

Hum Pathol. 1994 Dec;25(12):1346-51. doi: 10.1016/0046-8177(94)90096-5.


Tumor proliferation in bladder cancer is associated with tumor behavior. To assess the association between Ki-67 labeling index (LI), p53, and c-erbB-2 overexpression, formalin-fixed tissue samples of 160 patients with transitional cell carcinoma (TCC) of the urinary bladder were studied by immunohistochemistry. Ki-67 LI was strongly associated with tumor stage (P < .0001), tumor grade (P < .0001), and p53 status (P = .0014) but not with erbB-2 overexpression (P > .2). Ki-67 LI was higher in p53-positive tumors (19%) than in p53-negative tumors (14%) when all stages were compared. Ki-67 LI was independent of p53 expression in pTa tumors (p53-positive, 9%; p53-negative, 11%), showing that p53 overexpression alone is not sufficient to induce rapid tumor cell proliferation in pTa tumors. Ki-67 LI also was independent of p53 expression in pT2 to pT4 tumors (p53-positive, 20%; p53-negative, 23%), indicating that p53 expression is not necessary for rapid tumor cell proliferation in advanced stages. However, there was a striking difference in Ki-67 LI between p53-positive pT1 tumors (22.0% +/- 8.8 standard deviation [SD]; n = 20) and p53-negative pT1 tumors (9.7 +/- 8.3 SD; n = 22; P = .0001). These results suggest that increased proliferation in p53-positive pT1 tumors is caused by additional alterations that occur during tumor progression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Carcinoma, Transitional Cell / genetics
  • Carcinoma, Transitional Cell / metabolism*
  • Carcinoma, Transitional Cell / pathology*
  • Carcinoma, Transitional Cell / secondary
  • Gene Expression
  • Humans
  • Ki-67 Antigen
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / pathology*


  • Ki-67 Antigen
  • Neoplasm Proteins
  • Nuclear Proteins
  • Tumor Suppressor Protein p53
  • Receptor, ErbB-2