Bilharzial related, organ confined, muscle invasive bladder cancer: prognostic value of apoptosis markers, proliferation markers, p53, E-cadherin, epidermal growth factor receptor and c-erbB-2.
OBJECTIVE
We investigated the association of the apoptosis related proteins Bcl-2, Bcl-x, Bax and Bak, p53, the adhesion molecule E-cadherin, the receptor proteins epidermal growth factor receptor and c-erbB-2, and the proliferation markers proliferating cell nuclear antigen and Ki-67 with the clinical outcome of bilharzial related transitional cell carcinoma and squamous cell carcinoma.


METHODS
Cystectomy specimens from 109 patients with organ confined, muscle invasive stage, pT2pN0M0, bilharziall positive bladder cancer were examined, including 60 with squamous cell carcinoma and 49 with transitional cell carcinoma. Immunohistochemical results were correlated with tumor progression.


RESULTS
In squamous cell carcinoma but not in transitional cell carcinoma the loss of epidermal growth factor receptor, Bax and Bak was significantly associated with higher histological grade (p = 0.02, 0.006 and 0.01, respectively). On univariate analysis patients with transitional cell carcinoma had a poorer prognosis than those with squamous cell carcinoma. p53 Over expression and the loss of Bak positivity were associated with shortened progression-free survival in transitional cell carcinoma (p = 0.006 and 0.04, respectively), and squamous cell carcinoma (p = 0.00001 and 0.04, respectively). In squamous cell carcinoma high tumor grade (p = 0.02) and in transitional cell carcinoma high labeling indexes for MIB-1, Bcl-x expression and c-erbB-2 positivity (p = 0.03, 0.02 and 0.04, respectively) were associated with a poorer prognosis. On multivariate analysis p53 emerged as a significant prognostic factor for each condition. Additional independent prognostic factors were proliferating cell nuclear antigen for squamous cell carcinoma, and MIB-1, Bcl-x and Bax for transitional cell carcinoma.


CONCLUSIONS
Bilharzial related transitional cell carcinoma and squamous cell carcinoma of the bladder differ in interims of protein expression and prognosis. Independent prognostic factors were p53, MIB-1, Bcl-x, and Bax in the former disease, and p53 and proliferating cell nuclear antigen in the latter disease.
Haitel
A
A
Departments of Urology and Pathology, University of Vienna, Austria, and Urology and Nephrology Center, Mansoura, Egypt.
Posch
B
B
El-Baz
M
M
Mokhtar
A A
AA
Susani
M
M
Ghoneim
M A
MA
Marberger
M
M
D000328:Adult; D000368:Aged; D034961:Antigens, Nuclear; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis*; D015820:Cadherins / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D002295:Carcinoma, Transitional Cell / Q000150:complications / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D002455:Cell Division; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D008875:Middle Aged; D009687:Nuclear Proteins / Q000032:analysis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D012553:Schistosomiasis haematobia / Q000150:complications*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D001749:Urinary Bladder Neoplasms / Q000150:complications / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
D034961:Antigens, Nuclear; D014408:Biomarkers, Tumor; D015820:Cadherins; D066246:ErbB Receptors; D019394:Ki-67 Antigen; D008565:Membrane Proteins; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; C494772:BAK1 protein, human; C494826:BAX protein, human; C494811:BCL2L1 protein, human