Expression of cell cycle-related molecular markers in patients treated with radical cystectomy for squamous cell carcinoma of the bladder.
We evaluated the association of p53, p21, p27, cyclin E, and Ki-67 expression with pathologic features and clinical outcomes of patients with squamous cell carcinoma (SCC) of the urinary bladder. Immunohistochemical staining was performed on radical cystectomy specimens with pure SCC from 1997 to 2003. Bright field microscopy imaging coupled with advanced color detection software was used. The relationship between these markers and pathologic parameters as well as clinical outcome was assessed. The study included 152 patients (80.9% with bilharziasis), 99 males and 53 females, with a median age of 51 years (range, 36-74 years). The presenting stage was T2 or higher, and the presenting grade was grade II or lower in 93.4% of patients. Altered cyclin E expression was associated with stages (P = .02), altered p21 with grades (P = .02), and altered p27 with lymphovascular invasion (P = .01). In multivariable analyses, altered p53 expression was the only marker associated with an increased risk of disease recurrence (hazards ratio, 1.77; 95% confidence interval, 1.03-3.38, P = .04; and hazards ratio, 2.28; 95% confidence interval, 1.01-5.70, P = .05) and bladder cancer-specific mortality (hazards ratio, 1.76; 95% confidence interval, 1.06-2.99, P = .05, and hazards ratio, 2.64; 95% confidence interval, 1.05-5.54, P = .05) in all patients and in patients with T1-3N0 tumors, respectively. In conclusion, cell cycle-related molecular markers are commonly altered in SCC of the urinary bladder. Only p53 had a prognostic role in patients treated with radical cystectomy for SCC. Our findings support the need for further evaluation of molecular markers and their signaling pathways in SCC.
Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9110, USA.
Ramy F
RF
Youssef
Shahrokh F
SF
Shariat
Payal
P
Kapur
Wareef
W
Kabbani
Tarek
T
Ghoneim
Ellen
E
King
Amber
A
Cockburn
Ahmed
A
Mosbah
Hassan
H
Abol-Enein
Mohamed
M
Ghoneim
Yair
Y
Lotan
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000601:surgery; D018797:Cell Cycle Proteins / Q000378:metabolism*; D019927:Cyclin E / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D015653:Cystectomy; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012552:Schistosomiasis; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000601:surgery
D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53; C413374:p27 antigen