Non-endothelial KDR/flk-1 expression is associated with increased survival of patients with urothelial bladder carcinomas.
OBJECTIVE
To investigate the immunohistochemical expression of KDR/flk-1 in a series of 114 urothelial bladder carcinomas in relation to clinicopathological parameters, Ki67, p53 and Bcl-2 protein expression and patient survival. KDR/flk-1 is a high-affinity tyrosine kinase receptor for vascular endothelial growth factor (VEGF), on vascular endothelium. However, there is increasing evidence that KDR/flk-1 is also expressed by normal non-endothelial and tumour cells.


RESULTS
Immunohistochemistry was performed on paraffin sections using monoclonal and polyclonal antibodies. Statistical analysis was univariate (chi2 log rank test) and multivariate (Cox's model). KDR/flk-1 expression was observed in the cytoplasm of cancerous cells in 68.4% of cases. No statistically significant associations were observed between KDR/flk-1 expression and grade or stage of urothelial carcinomas, Ki67, p53 or Bcl-2 expression. In contrast, widespread KDR/flk-1 expression in more than 50% of cancerous cells was associated with increased survival, on univariate and multivariate analysis (P = 0.0119 and P = 0.042, respectively).


CONCLUSIONS
Although the biological significance of non-endothelial KDR/flk-1 expression has not yet been elucidated, its association with better patient survival may be related to the failure of non-endothelial KDR/flk-1 to mediate angiogenic and mitogenic effects.
Gakiopoulou-Givalou
H
H
Department of Pathology, Medical School, Laikon Hospital, University of Athens, Athens, Greece.
Nakopoulou
L
L
Panayotopoulou
E G
EG
Zervas
A
A
Mavrommatis
J
J
Giannopoulos
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000378:metabolism / Q000401:mortality*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000401:mortality*; D019459:Urothelium / Q000473:pathology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D040301:Vascular Endothelial Growth Factor Receptor-2