Translational research in bladder cancer: From molecular pathogenesis to useful tissue biomarkers

Cancer Biology and Therapy

Volumn 10, Issue 5, 2010, Pages 407-415

  Bolenz, Christian ^a,b   Lotan, Yair ^a  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^b UNIVERSITY OF HEIDELBERG   (Germany)

Author keywords

Biological markers; Bladder cancer; Molecular pathogenesis; Prediction; Prognosis; Treatment protocols

Indexed keywords

BCG VACCINE; CARBOPLATIN; CASPASE 3; CYCLIN D1; CYCLIN DEPENDENT KINASE INHIBITOR 2A; CYCLIN E; EPIDERMAL GROWTH FACTOR RECEPTOR 2; FIBROBLAST GROWTH FACTOR RECEPTOR 3; GEMCITABINE; KI 67 ANTIGEN; MATRILYSIN; MICRORNA; MITOGEN ACTIVATED PROTEIN KINASE; PACLITAXEL; PROTEIN BAX; PROTEIN BCL 2; PROTEIN P21; PROTEIN P27; PROTEIN P53; SCATTER FACTOR; SCATTER FACTOR RECEPTOR; SURVIVIN; THROMBOSPONDIN 1; TRASTUZUMAB; UVOMORULIN; VASCULOTROPIN;

ACCURACY; ANGIOGENESIS; APOPTOSIS; BLADDER CARCINOMA; CANCER CELL CULTURE; CANCER CHEMOTHERAPY; CANCER GROWTH; CANCER RECURRENCE; CANCER SURVIVAL; CELL CYCLE PROGRESSION; CELL CYCLE REGULATION; CELL GROWTH; CELL INVASION; CELL MIGRATION; CHROMOSOME 17; CHROMOSOME 3; CHROMOSOME 7; CHROMOSOME 9P; CHROMOSOME 9Q; CHROMOSOME ABERRATION; CPG ISLAND; ENZYME ACTIVITY; EXTRACELLULAR MATRIX; FLUORESCENCE IN SITU HYBRIDIZATION; GENE EXPRESSION PROFILING; GENE MUTATION; HETEROZYGOSITY LOSS; HUMAN; IMMUNOHISTOCHEMISTRY; NONHUMAN; OVERALL SURVIVAL; PATHOGENESIS; PROTEIN EXPRESSION; REVIEW; SENSITIVITY AND SPECIFICITY; SIGNAL TRANSDUCTION; TISSUE MICROARRAY; TRANSURETHRAL RESECTION; TREATMENT RESPONSE; TUMOR GROWTH; UROTHELIAL CARCINOMA OF THE BLADDER; VALIDATION STUDY;

ANTINEOPLASTIC PROTOCOLS; APOPTOSIS; CELL CYCLE; CELL PROLIFERATION; GENETIC MARKERS; HUMANS; NEOPLASM INVASIVENESS; NEOVASCULARIZATION, PATHOLOGIC; PROGNOSIS; RISK; SIGNAL TRANSDUCTION; TUMOR MARKERS, BIOLOGICAL; URINARY BLADDER NEOPLASMS;

EID: 77957110450     PISSN: 15384047     EISSN: 15558576     Source Type: Journal    
DOI: 10.4161/cbt.10.5.13022     Document Type: Review

References (125)

1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics 2009. CA Cancer J Clin 2009; 59:225-49.
2. Mitra AP, Datar RH, Cote RJ. Molecular pathways in invasive bladder cancer: new insights into mechanisms, progression and target identification. J Clin Oncol 2006; 24:5552-64.
3. Sylvester RJ, van der Meijden AP, Oosterlinck W, Witjes JA, Bouffioux C, Denis L, et al. Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2,596 patients from seven EORTC trials. Eur Urol 2006; 49:466-75. (Pubitemid 43259554)
4. Shariat SF, Karakiewicz PI, Palapattu GS, Lotan Y, Rogers CG, Amiel GE, et al. Outcomes of radical cystectomy for transitional cell carcinoma of the bladder: a contemporary series from the Bladder Cancer Research Consortium. J Urol 2006; 176:2414-22.
5. Stein JP, Lieskovsky G, Cote R, Groshen S, Feng AC, Boyd S, et al. Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. J Clin Oncol 2001; 19:666-75. (Pubitemid 32120143)
6. Bochner BH, Kattan MW, Vora KC. Postoperative nomogram predicting risk of recurrence after radical cystectomy for bladder cancer. J Clin Oncol 2006; 24:3967-72.
7. Karakiewicz PI, Shariat SF, Palapattu GS, Gilad AE, Lotan Y, Rogers CG, et al. Nomogram for predicting disease recurrence after radical cystectomy for transitional cell carcinoma of the bladder. J Urol 2006; 176:1354-61.
8. Shariat SF, Karakiewicz PI, Palapattu GS, Amiel GE, Lotan Y, Rogers CG, et al. Nomograms provide improved accuracy for predicting survival after radical cystectomy. Clin Cancer Res 2006; 12:6663-76.
9. Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data advanced bladder cancer (ABC) meta-analysis collaboration. Eur Urol 2005; 48:202-5.
10. Adjuvant chemotherapy for invasive bladder cancer (individual patient data). Cochrane Database Syst Rev 2006; 006018.
11. Freiha F, Reese J, Torti FM. A randomized trial of radical cystectomy versus radical cystectomy plus cisplatin, vinblastine and methotrexate chemotherapy for muscle invasive bladder cancer. J Urol 1996; 155:495-9. (Pubitemid 26023531)
12. Lehmann J, Franzaring L, Thuroff J, Wellek S, Stockle M. Complete long-term survival data from a trial of adjuvant chemotherapy vs. control after radical cystectomy for locally advanced bladder cancer. BJU Int 2006; 97:42-7.
13. Skinner DG, Daniels JR, Russell CA, Lieskovsky G, Boyd SD, Nichols P, et al. The role of adjuvant chemotherapy following cystectomy for invasive bladder cancer: a prospective comparative trial. J Urol 1991; 145:459-64.
14. Stockle M, Meyenburg W, Wellek S, Voges G, Gertenbach U, Thuroff JW, et al. Advanced bladder cancer (stages pT3b, pT4a, pN1 and pN2): improved survival after radical cystectomy and 3 adjuvant cycles of chemotherapy. Results of a controlled prospective study. J Urol 1992; 148:302-6.
15. David KA, Milowsky MI, Ritchey J, Carroll PR, Nanus DM. Low incidence of perioperative chemotherapy for stage III bladder cancer 1998 to 2003: a report from the National Cancer Data Base. J Urol 2007; 178:451-4.
16. Ilyin SE, Belkowski SM, Plata-Salaman CR. Biomarker discovery and validation: technologies and integrative approaches. Trends Biotechnol 2004; 22:411-6.
17. Bensalah K, Montorsi F, Shariat SF. Challenges of cancer biomarker profiling. Eur Urol 2007; 52:1601-9.
18. Egawa S, Kuruma H. Search for biomarkers of aggressiveness in bladder cancer. Eur Urol 2006; 50:20-2.
19. Karam JA, Lotan Y, Karakiewicz PI, Ashfaq R, Sagalowsky AI, Roehrborn CG, Shariat SF. Use of combined apoptosis biomarkers for prediction of bladder cancer recurrence and mortality after radical cystectomy. Lancet Oncol 2007; 8:128-36.
20. Shariat SF, Ashfaq R, Sagalowsky AI, Lotan Y. Predictive value of cell cycle biomarkers in nonmuscle invasive bladder transitional cell carcinoma. J Urol 2007; 177:481-7. (Pubitemid 46054033)
21. Shariat SF, Karakiewicz PI, Ashfaq R, Lerner SP, Palapattu GS, Cote RJ, et al. Multiple biomarkers improve prediction of bladder cancer recurrence and mortality in patients undergoing cystectomy. Cancer 2008; 112:315-25.
22. Shariat SF, Tokunaga H, Zhou J, Kim J, Ayala GE, Benedict WF, Lerner SP. p53, p21, pRB and p16 expression predict clinical outcome in cystectomy with bladder cancer. J Clin Oncol 2004; 22:1014-24.
23. Shariat SF, Zlotta AR, Ashfaq R, Sagalowsky AI, Lotan Y. Cooperative effect of cell cycle regulators expression on bladder cancer development and biologic aggressiveness. Mod Pathol 2007; 20:445-59.
24. Bolenz C, Lotan Y. Molecular biomarkers for urothelial carcinoma of the bladder: challenges in clinical use. Nat Clin Pract Urol 2008; 5:676-85.
25. Wu XR. Urothelial tumorigenesis: a tale of divergent pathways. Nat Rev Cancer 2005; 5:713-25.
26. Catto JW, Miah S, Owen HC, Bryant H, Myers K, Dudziec E, et al. Distinct microRNA alterations characterize high- and low-grade bladder cancer. Cancer Res 2009; 69:8472-81.
27. Mitra AP, Cote RJ. Molecular pathogenesis and diagnostics of bladder cancer. Annu Rev Pathol 2009; 4:251-85.
28. Sanchez-Garcia I. The crossroads of oncogenesis and metastasis. N Engl J Med 2009; 360:297-9.
29. Schulz WA. Understanding urothelial carcinoma through cancer pathways. Int J Cancer 2006; 119:1513-8.
30. Stoehr R, Zietz S, Burger M, Filbeck T, Denzinger S, Obermann EC, et al. Deletions of chromosomes 9 and 8p in histologically normal urothelium of patients with bladder cancer. Eur Urol 2005; 47:58-63.
31. Hartmann A, Schlake G, Zaak D, Hungerhuber E, Hofstetter A, Hofstaedter F, Knuechel R. Occurrence of chromosome 9 and p53 alterations in multifocal dysplasia and carcinoma in situ of human urinary bladder. Cancer Res 2002; 62:809-18. (Pubitemid 34126958)
32. Cairns P, Evron E, Okami K, Halachmi N, Esteller M, Herman JG, et al. Point mutation and homozygous deletion of PTEN/MMAC1 in primary bladder cancers. Oncogene 1998; 16:3215-8.
33. Zhu D, Xing D, Shen X, Liu J. A method to quantitatively detect H-ras point mutation based on electro-chemiluminescence. Biochem Biophys Res Commun 2004; 324:964-9.
34. van Rhijn BW, Montironi R, Zwarthoff EC, Jobsis AC, van der Kwast TH. Frequent FGFR3 mutations in urothelial papilloma. J Pathol 2002; 198:245-51. (Pubitemid 35243883)
35. Billerey C, Chopin D, Aubriot-Lorton MH, Ricol D, Gil Diez de Medina S, Van Rhijn B, et al. Frequent FGFR3 mutations in papillary non-invasive bladder (pTa) tumors. Am J Pathol 2001; 158:1955-9.
36. Cairns P, Proctor AJ, Knowles MA. Loss of heterozygosity at the RB locus is frequent and correlates with muscle invasion in bladder carcinoma. Oncogene 1991; 6:2305-9.
37. Cordon-Cardo C, Zhang ZF, Dalbagni G, Drobnjak M, Charytonowicz E, Hu SX, et al. Cooperative effects of p53 and pRB alterations in primary superficial bladder tumors. Cancer Res 1997; 57:1217-21.
38. Hartmann A, Moser K, Kriegmair M, Hofstetter A, Hofstaedter F, Knuechel R. Frequent genetic alterations in simple urothelial hyperplasias of the bladder in patients with papillary urothelial carcinoma. Am J Pathol 1999; 154:721-7. (Pubitemid 29122590)
39. Knowles MA. Molecular subtypes of bladder cancer: Jekyll and Hyde or chalk and cheese? Carcinogenesis 2006; 27:361-73.
40. Kruger S, Mess F, Bohle A, Feller AC. Numerical aberrations of chromosome 17 and the 9p21 locus are independent predictors of tumor recurrence in non-invasive transitional cell carcinoma of the urinary bladder. Int J Oncol 2003; 23:41-8.
41. Kawauchi S, Sakai H, Ikemoto K, Eguchi S, Nakao M, Takihara H, et al. 9p21 index as estimated by dual-color fluorescence in situ hybridization is useful to predict urothelial carcinoma recurrence in bladder washing cytology. Hum Pathol 2009; 40:1783-9.
42. Eguchi S, Yamamoto Y, Sakano S, Chochi Y, Nakao M, Kawauchi S, et al. The loss of 8p23.3 is a novel marker for predicting progression and recurrence of bladder tumors without muscle invasion. Cancer Genet Cytogenet 2010; 200:16-22.
43. Gonzalgo ML, Datar RH, Schoenberg MP, Cote RJ. The role of deoxyribonucleic acid methylation in development, diagnosis and prognosis of bladder cancer. Urol Oncol 2007; 25:228-35.
44. Aleman A, Cebrian V, Alvarez M, Lopez V, Orenes E, Lopez-Serra L, Algaba F, et al. Identification of PMF1 methylation in association with bladder cancer progression. Clin Cancer Res 2008; 14:8236-43.
45. Hernandez S, Lopez-Knowles E, Lloreta J, Kogevinas M, Jaramillo R, Amoros A, et al. FGFR3 and Tp53 mutations in T1G3 transitional bladder carcinomas: independent distribution and lack of association with prognosis. Clin Cancer Res 2005; 11:5444-50.
46. Mhawech-Fauceglia P, Fischer G, Alvarez V Jr, Ahmed A, Herrmann FR. Predicting outcome in minimally invasive (T1a and T1b) urothelial bladder carcinoma using a panel of biomarkers: a high throughput tissue microarray analysis. BJU Int 2007; 100:1182-7.
47. van Rhijn BW, Vis AN, van der Kwast TH, Kirkels WJ, Radvanyi F, Ooms EC, et al. Molecular grading of urothelial cell carcinoma with fibroblast growth factor receptor 3 and MIB-1 is superior to pathologic grade for the prediction of clinical outcome. J Clin Oncol 2003; 21:1912-21.
48. Burger M, van der Aa MN, van Oers JM, Brinkmann A, van der Kwast TH, Steyerberg EC, et al. Prediction of progression of non-muscle-invasive bladder cancer by WHO 1973 and 2004 grading and by FGFR3 mutation status: a prospective study. Eur Urol 2008; 54:835-43.
49. Zhang ZT, Pak J, Huang HY, Shapiro E, Sun TT, Pellicer A, Wu XR. Role of Ha-ras activation in superficial papillary pathway of urothelial tumor formation. Oncogene 2001; 20:1973-80. (Pubitemid 32458029)
50. Lindgren D, Frigyesi A, Gudjonsson S, Sjodahl G, Hallden C, Chebil G, Veerla S, et al. Combined gene expression and genomic profiling define two intrinsic molecular subtypes of urothelial carcinoma and gene signatures for molecular grading and outcome. Cancer Res 2010; 70:3463-72.
51. Birkhahn M, Mitra AP, Williams AJ, Lam G, Ye W, Datar RH, et al. Predicting recurrence and progression of noninvasive papillary bladder cancer at initial presentation based on quantitative gene expression profiles. Eur Urol 2010; 57:12-20.
52. Kim YJ, Ha YS, Kim SK, Yoon HY, Lym MS, Kim MJ, et al. Gene signatures for the prediction of response to bacillus calmette-guerin immunotherapy in primary pT1 bladder cancers. Clin Cancer Res 2010; 16:2131-7.
53. Benedict WF, Lerner SP, Zhou J, Shen X, Tokunaga H, Czerniak B. Level of retinoblastoma protein expression correlates with p16 (MTS-1/INK4A/CDKN2) status in bladder cancer. Oncogene 1999; 18:1197-203.
54. Chatterjee SJ, Datar R, Youssefzadeh D, George B, Goebell PJ, Stein JP, et al. Combined effects of p53, p21 and pRb expression in the progression of bladder transitional cell carcinoma. J Clin Oncol 2004; 22:1007-13.
55. Cordon-Cardo C, Wartinger D, Petrylak D, Dalbagni G, Fair WR, Fuks Z, Reuter VE. Altered expression of the retinoblastoma gene product: prognostic indicator in bladder cancer. J Natl Cancer Inst 1992; 84:1251-6.
56. Cote RJ, Dunn MD, Chatterjee SJ, Stein JP, Shi SR, Tran QC, et al. Elevated and absent pRb expression is associated with bladder cancer progression and has cooperative effects with p53. Cancer Res 1998; 58:1090-4.
57. Esrig D, Elmajian D, Groshen S, Freeman JA, Stein JP, Chen SC, et al. Accumulation of nuclear p53 and tumor progression in bladder cancer. N Engl J Med 1994; 331:1259-64.
58. Esrig D, Spruck CH, 3rd, Nichols PW, Chaiwun B, Steven K, Groshen S, et al. p53 nuclear protein accumulation correlates with mutations in the p53 gene, tumor grade and stage in bladder cancer. Am J Pathol 1993; 143:1389-97.
59. Grossman HB, Liebert M, Antelo M, Dinney CP, Hu SX, Palmer JL, Benedict WF. p53 and RB expression predict progression in T1 bladder cancer. Clin Cancer Res 1998; 4:829-34.
60. Sarkis AS, Dalbagni G, Cordon-Cardo C, Zhang ZF, Sheinfeld J, Fair WR, et al. Nuclear overexpression of p53 protein in transitional cell bladder carcinoma: a marker for disease progression. J Natl Cancer Inst 1993; 85:53-9.
61. WAF1/CIP1 expression on tumor progression in bladder cancer. J Natl Cancer Inst 1998; 90:1072-9.
62. Malats N, Bustos A, Nascimento CM, Fernandez F, Rivas M, Puente D, et al. p53 as a prognostic marker for bladder cancer: a meta-analysis and review. Lancet Oncol 2005; 6:678-86. (Pubitemid 41222758)
63. Shariat SF, Lotan Y, Karakiewicz PI, Ashfaq R, Isbarn H, Fradet Y, et al. p53 predictive value for pT1-2 N0 disease at radical cystectomy. J Urol 2009; 182:907-13.
64. Cote RJ, Esrig D, Groshen S, Jones PA, Skinner DG. p53 and treatment of bladder cancer. Nature 1997; 385:123-5.
65. Fleshner N, Kapusta L, Ezer D, Herschorn S, Klotz L. p53 nuclear accumulation is not associated with decreased disease-free survival in patients with node positive transitional cell carcinoma of the bladder. J Urol 2000; 164:1177-82.
66. Frank I, Cheville JC, Blute ML, Lohse CM, Karnes RJ, Weaver AL, et al. Prognostic value of p53 and MIB-1 in transitional cell carcinoma of the urinary bladder with regional lymph node involvement. Cancer 2004; 101:1803-8.
67. Lamy A, Gobet F, Laurent M, Blanchard F, Varin C, Moulin C, et al. Molecular profiling of bladder tumors based on the detection of FGFR3 and TP53 mutations. J Urol 2006; 176:2686-9.
68. Shariat SF, Bolenz C, Karakiewicz PI, Fradet Y, Ashfaq R, Bastian PJ, et al. p53 expression in patients with advanced urothelial cancer of the urinary bladder. BJU Int 2010; 105:489-95.
69. Yurakh AO, Ramos D, Calabuig-Farinas S, Lopez- Guerrero JA, Rubio J, Solsona E, et al. Molecular and immunohistochemical analysis of the prognostic value of cell cycle regulators in urothelial neoplasms of the bladder. Eur Urol 2006; 50:506-15; discussion 15.
70. Dalbagni G, Parekh DJ, Ben-Porat L, Potenzoni M, Herr HW, Reuter VE. Prospective evaluation of p53 as a prognostic marker in T1 transitional cell carcinoma of the bladder. BJU Int 2007; 99:281-5. (Pubitemid 46103104)
71. Lopez-Knowles E, Hernandez S, Kogevinas M, Lloreta J, Amoros A, Tardon A, et al. The p53 pathway and outcome among patients with T1G3 bladder tumors. Clin Cancer Res 2006; 12:6029-36.
72. Moonen PM, van Balken-Ory B, Kiemeney LA, Schalken JA, Witjes JA. Prognostic value of p53 for high risk superficial bladder cancer with long-term followup. J Urol 2007; 177:80-3.
73. George B, Datar RH, Wu L, Cai J, Patten N, Beil SJ, et al. p53 gene and protein status: the role of p53 alterations in predicting outcome in patients with bladder cancer. J Clin Oncol 2007; 25:5352-8.
74. Lerner SP. Bladder cancer clinical trials. Urol Oncol 2005; 23:275-9.
75. Lopez-Beltran A, Requena MJ, Luque RJ, Alvarez- Kindelan J, Quintero A, Blanca AM, et al. Cyclin D3 expression in primary Ta/T1 bladder cancer. J Pathol 2006; 209:106-13.
76. Shariat SF, Ashfaq R, Sagalowsky AI, Lotan Y. Association of cyclin D1 and E1 expression with disease progression and biomarkers in patients with nonmuscle-invasive urothelial cell carcinoma of the bladder. Urol Oncol 2007; 25:468-75. (Pubitemid 350151896)
77. Kamai T, Takagi K, Asami H, Ito Y, Oshima H, Yoshida KI. Decreasing of p27(Kip1)and cyclin E protein levels is associated with progression from superficial into invasive bladder cancer. Br J Cancer 2001; 84:1242-51.
78. Benedict WF, Xu HJ, Hu SX, Takahashi R. Role of the retinoblastoma gene in the initiation and progression of human cancer. J Clin Invest 1990; 85:988-93.
79. Logothetis CJ, Xu HJ, Ro JY, Hu SX, Sahin A, Ordonez N, Benedict WF. Altered expression of retinoblastoma protein and known prognostic variables in locally advanced bladder cancer. J Natl Cancer Inst 1992; 84:1256-61.
80. Cormio L, Tolve I, Annese P, Saracino A, Zamparese R, Sanguedolce F, et al. Altered p53 and pRb expression is predictive of response to BCG treatment in T1G3 bladder cancer. Anticancer Res 2009; 29:4201-4.
81. Yamana K, Bilim V, Hara N, Kasahara T, Itoi T, Maruyama R, et al. Prognostic impact of FAS/CD95/ APO-1 in urothelial cancers: decreased expression of Fas is associated with disease progression. Br J Cancer 2005; 93:544-51.
82. Akhtar M, Gallagher L, Rohan S. Survivin: role in diagnosis, prognosis and treatment of bladder cancer. Adv Anat Pathol 2006; 13:122-6. (Pubitemid 44341663)
83. Shariat SF, Ashfaq R, Karakiewicz PI, Saeedi O, Sagalowsky AI, Lotan Y. Survivin expression is associated with bladder cancer presence, stage, progression and mortality. Cancer 2007; 109:1106-13.
84. Li F. Role of survivin and its splice variants in tumorigenesis. Br J Cancer 2005; 92:212-6.
85. Kong G, Shin KY, Oh YH, Lee JJ, Park HY, Woo YN, Lee JD. Bcl-2 and p53 expressions in invasive bladder cancers. Acta Oncol 1998; 37:715-20.
86. L antisense oligodeoxynucleotides. Urol Oncol 2007; 25:476-82.
87. Cattoretti G, Becker MH, Key G, Duchrow M, Schluter C, Galle J, Gerdes J. Monoclonal antibodies against recombinant parts of the Ki-67 antigen (MIB 1 and MIB 3) detect proliferating cells in microwave-processed formalin-fixed paraffin sections. J Pathol 1992; 168:357-63. (Pubitemid 23013251)
88. Margulis V, Shariat SF, Ashfaq R, Sagalowsky AI, Lotan Y. Ki-67 is an independent predictor of bladder cancer outcome in patients treated with radical cystectomy for organ-confined disease. Clin Cancer Res 2006; 12:7369-73.
89. Margulis V, Lotan Y, Karakiewicz PI, Fradet Y, Ashfaq R, Capitanio U, Montorsi F, et al. Multi-institutional validation of the predictive value of Ki-67 labeling index in patients with urinary bladder cancer. J Natl Cancer Inst 2009; 101:114-9.
90. Canesin G, Gonzalez-Peramato P, Palou J, Urrutia M, Cordon-Cardo C, Sanchez-Carbayo M. Galectin-3 expression is associated with bladder cancer progression and clinical outcome. Tumour Biol 2010; 31:277-85.
91. Bolenz C, Shariat SF, Karakiewicz PI, Ashfaq R, Ho R, Sagalowsky AI, Lotan Y. Human epidermal growth factor receptor 2 expression status provides independent prognostic information in patients with urothelial carcinoma of the urinary bladder. BJU Int 2010.
92. Kruger S, Weitsch G, Buttner H, Matthiensen A, Bohmer T, Marquardt T, et al. HER2 overexpression in muscle-invasive urothelial carcinoma of the bladder: prognostic implications. Int J Cancer 2002; 102:514-8.
93. Lipponen P, Eskelinen M. Expression of epidermal growth factor receptor in bladder cancer as related to established prognostic factors, oncoprotein (c-erbB-2, p53) expression and long-term prognosis. Br J Cancer 1994; 69:1120-5. (Pubitemid 24161872)
94. Kassouf W, Black PC, Tuziak T, Bondaruk J, Lee S, Brown GA, et al. Distinctive expression pattern of ErbB family receptors signifies an aggressive variant of bladder cancer. J Urol 2008; 179:353-8.
95. Therasse P, Carbonnelle S, Bogaerts J. Clinical trials design and treatment tailoring: general principles applied to breast cancer research. Crit Rev Oncol Hematol 2006; 59:98-105.
96. Gandour-Edwards R, Lara PN Jr, Folkins AK, LaSalle JM, Beckett L, Li Y, et al. Does HER2/neu expression provide prognostic information in patients with advanced urothelial carcinoma? Cancer 2002; 95:1009-15.
97. Bellmunt J, Albiol S, Suarez C, Albanell J. Optimizing therapeutic strategies in advanced bladder cancer: Update on chemotherapy and the role of targeted agents. Crit Rev Oncol Hematol 2008; DOI:10.1016/j. critrevonc.2008.06.002.
98. Hussain MH, MacVicar GR, Petrylak DP, Dunn RL, Vaishampayan U, Lara PN Jr, et al. Trastuzumab, paclitaxel, carboplatin and gemcitabine in advanced human epidermal growth factor receptor-2/neu-positive urothelial carcinoma: results of a multicenter phase II National Cancer Institute trial. J Clin Oncol 2007; 25:2218-24.
99. Papathoma AS, Petraki C, Grigorakis A, Papakonstantinou H, Karavana V, Stefanakis S, et al. Prognostic significance of matrix metalloproteinases 2 and 9 in bladder cancer. Anticancer Res 2000; 20:2009-13.
100. Chambers AF, MacDonald IC, Schmidt EE, Koop S, Morris VL, Khokha R, Groom AC. Steps in tumor metastasis: new concepts from intravital videomicroscopy. Cancer Metastasis Rev 1995; 14:279-301. (Pubitemid 26027931)
101. Jager T, Becker M, Eisenhardt A, Tilki D, Totsch M, Schmid KW, Romics I, et al. The prognostic value of cadherin switch in bladder cancer. Oncol Rep 2010; 23:1125-32.
102. Shariat SF, Pahlavan S, Baseman AG, Brown RM, Green AE, Wheeler TM, Lerner SP. E-cadherin expression predicts clinical outcome in carcinoma in situ of the urinary bladder. Urology 2001; 57:60-5.
103. Muramaki M, Miyake H, Terakawa T, Kumano M, Sakai I, Fujisawa M. Expression profile of E-cadherin and N-cadherin in non-muscle-invasive bladder cancer as a novel predictor of intravesical recurrence following transurethral resection. Urol Oncol 2010.
104. Chirco R, Liu XW, Jung KK, Kim HR. Novel functions of TIMPs in cell signaling. Cancer Metastasis Rev 2006; 25:99-113.
105. Svatek RS, Shah JB, Xing J, Chang D, Lin J, McConkey DJ, et al. A multiplexed, particle-based flow cytometric assay identified plasma matrix metalloproteinase-7 to be associated with cancer-related death among patients with bladder cancer. Cancer 2010; In press.
106. Gohji K, Fujimoto N, Ohkawa J, Fujii A, Nakajima M. Imbalance between serum matrix metalloproteinase-2 and its inhibitor as a predictor of recurrence of urothelial cancer. Br J Cancer 1998; 77:650-5. (Pubitemid 28059475)
107. Staack A, Badendieck S, Schnorr D, Loening SA, Jung K. Combined determination of plasma MMP2, MMP9 and TIMP1 improves the non-invasive detection of transitional cell carcinoma of the bladder. BMC Urol 2006; 6:19.
108. Davies B, Waxman J, Wasan H, Abel P, Williams G, Krausz T, et al. Levels of matrix metalloproteases in bladder cancer correlate with tumor grade and invasion. Cancer Res 1993; 53:5365-9.
109. Kanayama H, Yokota K, Kurokawa Y, Murakami Y, Nishitani M, Kagawa S. Prognostic values of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase- 2 expression in bladder cancer. Cancer 1998; 82:1359-66.
110. Durkan GC, Nutt JE, Marsh C, Rajjayabun PH, Robinson MC, Neal DE, Lunec J, Mellon JK. Alteration in urinary matrix metalloproteinase-9 to tissue inhibitor of metalloproteinase-1 ratio predicts recurrence in nonmuscle-invasive bladder cancer. Clin Cancer Res 2003; 9:2576-82.
111. Szarvas T, Becker M, vom Dorp F, Gethmann C, Totsch M, Bankfalvi A, et al. Matrix metalloproteinase- 7 as a marker of metastasis and predictor of poor survival in bladder cancer. Cancer Sci 2010; 101:1300-8.
112. Jeffers M, Schmidt L, Nakaigawa N, Webb CP, Weirich G, Kishida T, et al. Activating mutations for the met tyrosine kinase receptor in human cancer. Proc Natl Acad Sci USA 1997; 94:11445-50. (Pubitemid 27451018)
113. Endo K, Shirai A, Furukawa M, Yoshizaki T. Prognostic value of cell motility activation factors in patients with tongue squamous cell carcinoma. Hum Pathol 2006; 37:1111-6.
114. Miyata Y, Sagara Y, Kanda S, Hayashi T, Kanetake H. Phosphorylated hepatocyte growth factor receptor/c- Met is associated with tumor growth and prognosis in patients with bladder cancer: correlation with matrix metalloproteinase-2 and -7 and E-cadherin. Hum Pathol 2009; 40:496-504.
115. Theodorescu D, Sapinoso LM, Conaway MR, Oxford G, Hampton GM, Frierson HF Jr. Reduced expression of metastasis suppressor RhoGDI2 is associated with decreased survival for patients with bladder cancer. Clin Cancer Res 2004; 10:3800-6.
116. Bochner BH, Cote RJ, Weidner N, Groshen S, Chen SC, Skinner DG, Nichols PW. Angiogenesis in bladder cancer: relationship between microvessel density and tumor prognosis. J Natl Cancer Inst 1995; 87:1603-12.
117. Shariat SF, Youssef RF, Gupta A, Chade DC, Karakiewicz PI, Isbarn H, et al. Association of angiogenesis related markers with bladder cancer outcomes and other molecular markers. J Urol 183:1744-50.
118. Herrmann E, Eltze E, Bierer S, Kopke T, Gorge T, Neumann J, et al. VEGF-C, VEGF-D and Flt-4 in transitional bladder cancer: relationships to clinicopathological parameters and long-term survival. Anticancer Res 2007; 27:3127-33.
119. Crew JP, O'Brien T, Bradburn M, Fuggle S, Bicknell R, Cranston D, Harris AL. Vascular endothelial growth factor is a predictor of relapse and stage progression in superficial bladder cancer. Cancer Res 1997; 57:5281-5. (Pubitemid 27516364)
120. Xia G, Kumar SR, Hawes D, Cai J, Hassanieh L, Groshen S, et al. Expression and significance of vascular endothelial growth factor receptor 2 in bladder cancer. J Urol 2006; 175:1245-52.
121. Ioachim E, Michael MC, Salmas M, Damala K, Tsanou E, Michael MM, et al. Thrombospondin-1 expression in urothelial carcinoma: prognostic significance and association with p53 alterations, tumour angiogenesis and extracellular matrix components. BMC Cancer 2006; 6:140.
122. Grossfeld GD, Ginsberg DA, Stein JP, Bochner BH, Esrig D, Groshen S, et al. Thrombospondin-1 expression in bladder cancer: association with p53 alterations, tumor angiogenesis and tumor progression. J Natl Cancer Inst 1997; 89:219-27.
123. Giuriato S, Ryeom S, Fan AC, Bachireddy P, Lynch RC, Rioth MJ, et al. Sustained regression of tumors upon MYC inactivation requires p53 or thrombospondin-1 to reverse the angiogenic switch. Proc Natl Acad Sci USA 2006; 103:16266-71.
124. Shariat SF, Kim J, Raptidis G, Ayala GE, Lerner SP. Association of p53 and p21 expression with clinical outcome in patients with carcinoma in situ of the urinary bladder. Urology 2003; 61:1140-5. (Pubitemid 36693989)
125. Shariat SF, Karakiewicz PI, Fradet I, Ashfaq R, Stein JP, Bastian PJMEN, et al. Combination of cell cycle regulating bio-markers improves prognosis in patients with organ confined urothelial cancer at radical cystectomy. J Urol 2008; 179:578.