Abnormal expression of multiple proteins predicts cancer-specific mortality in patients with high-grade non-muscle-invasive bladder cancer treated with transurethral resection

被引:4
作者
Tsumura, Hideyasu [1 ]
Matsumoto, Kazumasa [1 ]
Sato, Yuichi [2 ]
Ikeda, Masaomi [1 ]
Fujita, Tetsuo [1 ]
Satoh, Takefumi [1 ]
Iwamura, Masatsugu [1 ]
机构
[1] Kitasato Univ, Sch Med, Dept Urol, Sagamihara, Kanagawa 2520374, Japan
[2] Kitasato Univ, Sch Allied Hlth Sci, Dept Mol Diagnost, Sagamihara, Kanagawa 2520374, Japan
关键词
bladder cancer; high-grade; non-muscle-invasive bladder cancer; survival; immunohistochemistry;
D O I
10.3892/mco.2013.92
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
High-grade non-muscle-invasive bladder urothelial carcinoma leads to various outcomes. It can cause death even after radical cystectomy and is treated only by transurethral resection (TUR). In the present study, we aimed to determine whether the molecular markers E-cadherin, coxsackie adenovirus receptor (CAR), S100A4 and uroplakin III are associated with clinicopathological outcomes in patients with high-grade non-muscle invasive bladder cancer (NMIBC) treated with TUR. Immunohistochemical staining was performed on serial sections from specimens obtained from 77 patients. Expression patterns were stratified according to the number of abnormally expressed markers: 0-1 or =2. The median follow-up time was 56 months (range, 3-287). The results from the present study indicated that expression of E-cadherin, CAR, S100A4 and uroplakin III was abnormal in 16, 17, 27 and 61% of tumors, respectively. Results of the log-rank test revealed that patients with abnormal expression of multiple molecular markers had a significantly increased risk of bladder cancer-specific mortality (P=0.016). The 5-year cancer-specific survival rates were 91 and 66% for patients with 0-1 and =2 molecular markers, respectively. No individual marker was associated with disease prognosis. Multivariate models that included clinicopathological outcomes and classified molecular markers indicated that abnormal expression of multiple molecular markers and lack of bacillus Calmette-Guerin (BCG) instillation are predictors of cancer-specific death (P=0.046 and 0.029, respectively). Abnormal expression of multiple molecular markers is a strong predictor of mortality in bladder cancer patients undergoing TUR, suggesting that high-grade non-muscle-invasive cancer is characterized by a variety of pathophysiological pathways. A combination of molecular markers may be useful in a minimally invasive modality for determining prognosis.
引用
收藏
页码:473 / 479
页数:7
相关论文
共 26 条
[1]   Focal S100A4 protein expression is an independent predictor of development of metastatic disease in cystectomized bladder cancer patients [J].
Agerbaek, Mads ;
Aisner, Jan ;
Marcussen, Niels ;
Lundbeck, Finn ;
Von Der Maase, Hans .
EUROPEAN UROLOGY, 2006, 50 (04) :777-785
[2]   Myopodin Methylation is Associated With Clinical Outcome in Patients With T1G3 Bladder Cancer [J].
Alvarez-Mugica, Miguel ;
Cebrian, Virginia ;
Fernandez-Gomez, Jesus M. ;
Fresno, Florentino ;
Escaf, Safwan ;
Sanchez-Carbayo, Marta .
JOURNAL OF UROLOGY, 2010, 184 (04) :1507-1513
[3]   Expression of S100A4 combined with reduced E-cadherin expression predicts patient outcome in malignant melanoma [J].
Andersen, K ;
Nesland, JM ;
Holm, R ;
Florenes, VA ;
Fodstad, O ;
Mælandsmo, GM .
MODERN PATHOLOGY, 2004, 17 (08) :990-997
[4]   Maintenance bacillus Calmette-Guerin in high-risk nonmuscle-invasive bladder cancer - How much is enough? [J].
Decobert, Marc ;
LaRue, Helene ;
Harel, Francois ;
Meyer, Francois ;
Fradet, Yves ;
Lacombe, Louis .
CANCER, 2008, 113 (04) :710-716
[5]  
Heimann R, 2000, CANCER RES, V60, P298
[6]   A re-staging transurethral resection predicts early progression of superficial bladder cancer [J].
Herr, Harry W. ;
Donat, S. Machele .
BJU INTERNATIONAL, 2006, 97 (06) :1194-1198
[7]   Does early cystectomy improve the survival of patients with high risk superficial bladder tumors? [J].
Herr, HW ;
Sogani, PC .
JOURNAL OF UROLOGY, 2001, 166 (04) :1296-1299
[8]   Persistent uroplakin expression in advanced urothelial carcinomas: implications in urothelial tumor progression and clinical outcome [J].
Huang, Hong-Ying ;
Shariat, Shahrokh F. ;
Sun, Tung-Tien ;
Lepor, Herbert ;
Shapiro, Ellen ;
Hsieh, Jer-Tsong ;
Ashfaq, Raheela ;
Lotan, Yair ;
Wu, Xue-Ru .
HUMAN PATHOLOGY, 2007, 38 (11) :1703-1713
[9]   Overexpression of p53 protein in a high-risk population of patients with superficial bladder cancer before and after Bacillus Calmette-Guerin therapy: Correlation to clinical outcome [J].
Lacombe, L ;
Dalbagni, G ;
Zhang, ZF ;
CordonCardo, C ;
Fair, WR ;
Herr, HW ;
Reuter, VE .
JOURNAL OF CLINICAL ONCOLOGY, 1996, 14 (10) :2646-2652
[10]   Maintenance bacillus Calmette-Guerin immunotherapy for recurrent Ta, T1 and carcinoma in situ transitional cell carcinoma of the bladder: A randomized Southwest Oncology Group study [J].
Lamm, DL ;
Blumenstein, BA ;
Crissman, JD ;
Montie, JE ;
Gottesman, JE ;
Lowe, BA ;
Sarosdy, MF ;
Bohl, RD ;
Grossman, HB ;
Beck, TM ;
Leimert, JT ;
Crawford, ED .
JOURNAL OF UROLOGY, 2000, 163 (04) :1124-1129