p53 but not erbB-2 expression is associated with rapid tumor proliferation in urinary bladder cancer.
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.
Moch
H
H
Department of Pathology, University of Basel, Switzerland.
Sauter
G
G
Mihatsch
M J
MJ
Gudat
F
F
Epper
R
R
Waldman
F M
FM
D002295:Carcinoma, Transitional Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000556:secondary; D015870:Gene Expression; D006801:Humans; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53