Expression of p21(waf1/cip1) protein in transitional cell bladder tumours and its prognostic value.
OBJECTIVE
p21(waf1/cip1) protein is a cyclin-dependent kinase inhibitor able to arrest the cell at the G1 phase by inhibiting DNA replication through interaction with proliferating cell nuclear antigen (PCNA). Experimental analyses of human bladder cancer cell lines show that p21 might be considered a tumour suppressor gene since it is able to induce apoptosis like p53. The prognostic value and expression of p21(waf1/cip1) is incompletely studied in bladder cancer at present.


METHODS
The expression of p21 protein was immunohistochemically analysed in paraffin-embedded specimens of 186 patients with primary transitional cell bladder tumours. The results of immunohistochemical analysis were related to known prognostic factors and complete long clinical follow-up data (over 11 years).


RESULTS
The expression of p21(waf1/cip1) protein was significantly related to DNA ploidy, S phase fraction, mitotic index, apoptotic index, morphometric nuclear factors, and the expression of p53 and PCNA proteins, whereas it was unrelated to grade or TNM classification. In univariate survival analysis, the expression of p21(waf1/cip1) protein was not significantly related to prognosis. Independent prognostic factors were T category, papillary status and mitotic index.


CONCLUSIONS
The results indicate that although the expression of p21(waf1/cip1) protein is related to indicators of cell proliferation, apoptosis and p53 expression, it has no better prognostic value than already established prognostic factors in bladder cancer.
Lipponen
P
P
Department of Pathology and Forensic Medicine, University of Kuopio, Kuopio, Finland. pertti.lipponen@kuopio.fi
Aaltomaa
S
S
Eskelinen
M
M
Ala-Opas
M
M
Kosma
V M
VM
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002295:Carcinoma, Transitional Cell / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D002455:Cell Division; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D016213:Cyclins / Q000032:analysis*; D004791:Enzyme Inhibitors / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D001749:Urinary Bladder Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology
D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D016159:Tumor Suppressor Protein p53; D018844:Cyclin-Dependent Kinases