Urologic Oncology: Seminars and Original Investigations
Volume 26, Issue 2 , Pages 113-124 , March 2008

Molecular markers for predicting prognosis of renal cell carcinoma

Received 8 February 2007 ,Revised 8 March 2007 ,Accepted 15 March 2007.

References 

  1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2007. CA Cancer J Clin. 2007;57:43–66
  2. Levy DA, Slaton JW, Swanson DA, et al. Stage specific guidelines for surveillance after radical nephrectomy for local renal cell carcinoma. J Urol. 1998;159:1163–1167
  3. Pantuck AJ, Zisman A, Belldegrun AS. The changing natural history of renal cell carcinoma. J Urol. 2001;166:1611–1623
  4. Figlin RA. Renal cell carcinoma: Management of advanced disease. J Urol. 1999;161:381–386Discussion 6–7
  5. Young AN, Amin MB, Moreno CS, et al. Expression profiling of renal epithelial neoplasms: A method for tumor classification and discovery of diagnostic molecular markers. Am J Pathol. 2001;158:1639–1651
  6. Young AN, de Oliveira-Salles PG, Lim SD, et al. βDefensin-1, parvalbumin, and vimentin: A panel of diagnostic immunohistochemical markers for renal tumors derived from gene expression profiling studies using cDNA microarrays. Am J Surg Pathol. 2003;27:199–205
  7. Zhou M, Roma A, Magi-Galluzzi C. The usefulness of immunohistochemical markers in the differential diagnosis of renal neoplasms. Clin Lab Med. 2005;25:247–257
  8. Takahashi M, Rhodes DR, Furge KA, et al. Gene expression profiling of clear cell renal cell carcinoma: Gene identification and prognostic classification. Proc Natl Acad Sci USA. 2001;98:9754–9759
  9. Vasselli JR, Shih JH, Iyengar SR, et al. Predicting survival in patients with metastatic kidney cancer by gene-expression profiling in the primary tumor. Proc Natl Acad Sci USA. 2003;100:6958–6963
  10. Sultmann H, von Heydebreck A, Huber W, et al. Gene expression in kidney cancer is associated with cytogenetic abnormalities, metastasis formation, and patient survival. Clin Cancer Res. 2005;11:646–655
  11. Kosari F, Parker AS, Kube DM, et al. Clear cell renal cell carcinoma: Gene expression analyses identify a potential signature for tumor aggressiveness. Clin Cancer Res. 2005;11:5128–5139
  12. Jones J, Otu H, Spentzos D, et al. Gene signatures of progression and metastasis in renal cell cancer. Clin Cancer Res. 2005;11:5730–5739
  13. Ramaswamy S, Ross KN, Lander ES, et al. A molecular signature of metastasis in primary solid tumors. Nat Genet. 2003;33:49–54
  14. Zhao H, Ljungberg B, Grankvist K, et al. Gene expression profiling predicts survival in conventional renal cell carcinoma. PLoS Med. 2006;3:e13
  15. Wain HM, Lush M, Ducluzeau F, et al. Genew: The human gene nomenclature database. Nucleic Acids Res. 2002;30:169;Genew: The human gene nomenclature database 71. (Data retrieved January 2007).
  16. Gerdes J, Lemke H, Baisch H, et al. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol. 1984;133:1710–1715
  17. Zhang X, Takenaka I. Cell proliferation and apoptosis with BCL-2 expression in renal cell carcinoma. Urology. 2000;56:510–515
  18. Onda H, Yasuda M, Serizawa A, et al. Clinical outcome in localized renal cell carcinomas related to immunoexpression of proliferating cell nuclear antigen, Ki-67 antigen, and tumor size. Oncol Rep. 1999;6:1039–1043
  19. Moch H, Sauter G, Gasser TC, et al. p53 Protein expression but not mdm-2 protein expression is associated with rapid tumor cell proliferation and prognosis in renal cell carcinoma. Urol Res. 1997;25(Suppl 1):S25–S30
  20. Kallio JP, Hirvikoski P, Helin H, et al. Renal cell carcinoma MIB-1, Bax, and Bcl-2 expression and prognosis. J Urol. 2004;172:2158–2161
  21. Yildiz E, Gokce G, Kilicarslan H, et al. Prognostic value of the expression of Ki-67, CD44, and vascular endothelial growth factor and microvessel invasion, in renal cell carcinoma. BJU Int. 2004;93:1087–1093
  22. Tannapfel A, Hahn HA, Katalinic A, et al. Incidence of apoptosis, cell proliferation and P53 expression in renal cell carcinomas. Anticancer Res. 1997;17:1155–1162
  23. Aaltomaa S, Lipponen P, Ala-Opas M, et al. Expression of cyclins A and D and p21(waf1/cip1) proteins in renal cell cancer and their relation to clinicopathological variables and patient survival. Br J Cancer. 1999;80:2001–2007
  24. Rioux-Leclercq N, Turlin B, Bansard J, et al. Value of immunohistochemical Ki-67 and p53 determinations as predictive factors of outcome in renal cell carcinoma. Urology. 2000;55:501–505
  25. Bui MH, Visapaa H, Seligson D, et al. Prognostic value of carbonic anhydrase IX and KI67 as predictors of survival for renal clear cell carcinoma. J Urol. 2004;171:2461–2466
  26. Kim HL, Seligson D, Liu X, et al. Using protein expressions to predict survival in clear cell renal carcinoma. Clin Cancer Res. 2004;10:5464–5471
  27. Dudderidge TJ, Stoeber K, Loddo M, et al. Mcm2, geminin, and KI67 define proliferative state and are prognostic markers in renal cell carcinoma. Clin Cancer Res. 2005;11:2510–2517
  28. Cheville JC, Zincke H, Lohse CM, et al. pT1 clear cell renal cell carcinoma: A study of the association between MIB-1 proliferative activity and pathologic features and cancer specific survival. Cancer. 2002;94:2180–2184
  29. Gelb AB, Sudilovsky D, Wu CD, et al. Appraisal of intratumoral microvessel density, MIB-1 score, DNA content, and p53 protein expression as prognostic indicators in patients with locally confined renal cell carcinoma. Cancer. 1997;80:1768–1775
  30. Dimitrova DS, Prokhorova TA, Blow JJ, et al. Mammalian nuclei become licensed for DNA replication during late telophase. J Cell Sci. 2002;115:51–59
  31. Blow JJ, Hodgson B. Replication licensing—defining the proliferative state?. Trends Cell Biol. 2002;12:72–78
  32. Mendez J, Stillman B. Chromatin association of human origin recognition complex, cdc6, and minichromosome maintenance proteins during the cell cycle: Assembly of pre-replication complexes in late mitosis. Mol Cell Biol. 2000;20:8602–8612
  33. Wharton SB, Hibberd S, Eward KL, et al. DNA replication licensing and cell cycle kinetics of oligodendroglial tumors. Br J Cancer. 2004;91:262–269
  34. Stoeber K, Halsall I, Freeman A, et al. Immunoassay for urothelial cancers that detects DNA replication protein Mcm5 in urine. Lancet. 1999;354:1524–1525
  35. Stoeber K, Swinn R, Prevost AT, et al. Diagnosis of genito-urinary tract cancer by detection of minichromosome maintenance protein 5 in urine sediments. J Natl Cancer Inst. 2002;94:1071–1079
  36. Williams GH, Romanowski P, Morris L, et al. Improved cervical smear assessment using antibodies against proteins that regulate DNA replication. Proc Natl Acad Sci USA. 1998;95:14932–14937
  37. Meng MV, Grossfeld GD, Williams GH, et al. Minichromosome maintenance protein 2 expression in prostate: Characterization and association with outcome after therapy for cancer. Clin Cancer Res. 2001;7:2712–2718
  38. Wharton SB, Chan KK, Anderson JR, et al. Replicative Mcm2 protein as a novel proliferation marker in oligodendrogliomas and its relationship to Ki67 labelling index, histological grade and prognosis. Neuropathol Appl Neurobiol. 2001;27:305–313
  39. Kruger S, Thorns C, Stocker W, et al. Prognostic value of MCM2 immunoreactivity in stage T1 transitional cell carcinoma of the bladder. Eur Urol. 2003;43:138–145
  40. Stoeber K, Tlsty TD, Happerfield L, et al. DNA replication licensing and human cell proliferation. J Cell Sci. 2001;114:2027–2041
  41. Tabor CW, Tabor H. Polyamines. Annu Rev Biochem. 1984;53:749–790
  42. Pegg AE. Polyamine metabolism and its importance in neoplastic growth and a target for chemotherapy. Cancer Res. 1988;48:759–774
  43. Marton LJ, Pegg AE. Polyamines as targets for therapeutic intervention. Annu Rev Pharmacol Toxicol. 1995;35:55–91
  44. Scalabrino G, Ferioli ME. Polyamines in mammalian tumors (Part I). Adv Cancer Res. 1981;35:151–268
  45. Scalabrino G, Ferioli ME. Polyamines in mammalian tumors (Part II). Adv Cancer Res. 1982;36:1–102
  46. Rioux-Leclercq N, Delcros JG, Bansard JY, et al. Immunohistochemical analysis of tumor polyamines discriminates high-risk patients undergoing nephrectomy for renal cell carcinoma. Hum Pathol. 2004;35:1279–1284
  47. Levine AJ, Momand J, Finlay CA. The p53 tumour suppressor gene. Nature. 1991;351:453–456
  48. Greenblatt MS, Bennett WP, Hollstein M, et al. Mutations in the p53 tumor suppressor gene: Clues to cancer etiology and molecular pathogenesis. Cancer Res. 1994;54:4855–4878
  49. Harris CC. Structure and function of the p53 tumor suppressor gene: Clues for rational cancer therapeutic strategies. J Natl Cancer Inst. 1996;88:1442–1455
  50. Uchida T, Gao JP, Wang C, et al. Clinical significance of p53, mdm2, and bcl-2 proteins in renal cell carcinoma. Urology. 2002;59:615–620
  51. Shiina H, Igawa M, Urakami S, et al. Clinical significance of immunohistochemically detectable p53 protein in renal cell carcinoma. Eur Urol. 1997;31:73–80
  52. Uhlman DL, Nguyen PL, Manivel JC, et al. Association of immunohistochemical staining for p53 with metastatic progression and poor survival in patients with renal cell carcinoma. J Natl Cancer Inst. 1994;86:1470–1475
  53. Haitel A, Wiener HG, Baethge U, et al. mdm2 expression as a prognostic indicator in clear cell renal cell carcinoma: Comparison with p53 overexpression and clinicopathological parameters. Clin Cancer Res. 2000;6:1840–1844
  54. Zigeuner R, Ratschek M, Rehak P, et al. Value of p53 as a prognostic marker in histologic subtypes of renal cell carcinoma: A systematic analysis of primary and metastatic tumor tissue. Urology. 2004;63:651–655
  55. Shvarts O, Seligson D, Lam J, et al. p53 is an independent predictor of tumor recurrence and progression after nephrectomy in patients with localized renal cell carcinoma. J Urol. 2005;173:725–728
  56. Hofmockel G, Wittmann A, Dammrich J, et al. Expression of p53 and bcl-2 in primary locally confined renal cell carcinomas: No evidence for prognostic significance. Anticancer Res. 1996;16:3807–3811
  57. Bot FJ, Godschalk JC, Krishnadath KK, et al. Prognostic factors in renal-cell carcinoma: Immunohistochemical detection of p53 protein versus clinico-pathological parameters. Int J Cancer. 1994;57:634–637
  58. Lipponen P, Eskelinen M, Hietala K, et al. Expression of proliferating cell nuclear antigen (PC10), p53 protein and c-erbB-2 in renal adenocarcinoma. Int J Cancer. 1994;57:275–280
  59. Kim HL, Seligson D, Liu X, et al. Using tumor markers to predict the survival of patients with metastatic renal cell carcinoma. J Urol. 2005;173:1496–1501
  60. Lloyd RV, Erickson LA, Jin L, et al. p27kip1: A multifunctional cyclin-dependent kinase inhibitor with prognostic significance in human cancers. Am J Pathol. 1999;154:313–323
  61. Langner C, von Wasielewski R, Ratschek M, et al. Biological significance of p27 and Skp2 expression in renal cell carcinoma (A systematic analysis of primary and metastatic tumor tissues using a tissue microarray technique). Virchows Arch. 2004;445:631–636
  62. Hedberg Y, Davoodi E, Ljungberg B, et al. Cyclin E and p27 protein content in human renal cell carcinoma: Clinical outcome and associations with cyclin D. Int J Cancer. 2002;102:601–607
  63. Hedberg Y, Ljungberg B, Roos G, et al. Expression of cyclin D1, D3, E, and p27 in human renal cell carcinoma analyzed by tissue microarray. Br J Cancer. 2003;88:1417–1423
  64. Migita T, Oda Y, Naito S, et al. Low expression of p27(Kip1) is associated with tumor size and poor prognosis in patients with renal cell carcinoma. Cancer. 2002;94:973–979
  65. Haitel A, Wiener HG, Neudert B, et al. Expression of the cell cycle proteins p21, p27, and pRb in clear cell renal cell carcinoma and their prognostic significance. Urology. 2001;58:477–481
  66. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57–70
  67. Nolte C, Moos M, Schachner M. Immunolocalization of the neural cell adhesion molecule L1 in epithelia of rodents. Cell Tissue Res. 1999;298:261–273
  68. Brummendorf T, Kenwrick S, Rathjen FG. Neural cell recognition molecule L1: From cell biology to human hereditary brain malformations. Curr Opin Neurobiol. 1998;8:87–97
  69. Elias DJ, Kline LE, Robbins BA, et al. Monoclonal antibody KS1/4-methotrexate immunoconjugate studies in non-small cell lung carcinoma. Am J Respir Crit Care Med. 1994;150:1114–1122
  70. Pancook JD, Reisfeld RA, Varki N, et al. Expression and regulation of the neural cell adhesion molecule L1 on human cells of myelomonocytic and lymphoid origin. J Immunol. 1997;158:4413–4421
  71. Kamiguchi H, Lemmon V. Neural cell adhesion molecule L1: Signaling pathways and growth cone motility. J Neurosci Res. 1997;49:1–8
  72. Brummendorf T, Lemmon V. Immunoglobulin superfamily receptors: Cis-interactions, intracellular adapters, and alternative splicing regulate adhesion. Curr Opin Cell Biol. 2001;13:611–618
  73. Fogel M, Gutwein P, Mechtersheimer S, et al. L1 expression as a predictor of progression and survival in patients with uterine and ovarian carcinomas. Lancet. 2003;362:869–875
  74. Fogel M, Mechtersheimer S, Huszar M, et al. L1 adhesion molecule (CD 171) in development and progression of human malignant melanoma. Cancer Lett. 2003;189:237–247
  75. Deichmann M, Kurzen H, Egner U, et al. Adhesion molecules CD171 (L1CAM) and CD24 are expressed by primary neuroendocrine carcinomas of the skin (Merkel cell carcinomas). J Cutan Pathol. 2003;30:363–368
  76. Thies A, Schachner M, Moll I, et al. Overexpression of the cell adhesion molecule L1 is associated with metastasis in cutaneous malignant melanoma. Eur J Cancer. 2002;38:1708–1716
  77. Miyahara R, Tanaka F, Nakagawa T, et al. Expression of neural cell adhesion molecules (polysialylated form of neural cell adhesion molecule and L1-cell adhesion molecule) on resected small cell lung cancer specimens: In relation to proliferation state. J Surg Oncol. 2001;77:49–54
  78. Allory Y, Matsuoka Y, Bazille C, et al. The L1 cell adhesion molecule is induced in renal cancer cells and correlates with metastasis in clear cell carcinomas. Clin Cancer Res. 2005;11:1190–1197
  79. Merseburger AS, Hennenlotter J, Simon P, et al. Cathepsin D expression in renal cell cancer-clinical implications. Eur Urol. 2005;48:519–526
  80. Islam R, Kristiansen LV, Romani S, et al. Activation of EGF receptor kinase by L1-mediated homophilic cell interactions. Mol Biol Cell. 2004;15:2003–2012
  81. Balzar M, Briaire-de Bruijn IH, Rees-Bakker HA, et al. Epidermal growth factor-like repeats mediate lateral and reciprocal interactions of Ep-CAM molecules in homophilic adhesions. Mol Cell Biol. 2001;21:2570–2580
  82. Momburg F, Moldenhauer G, Hammerling GJ, et al. Immunohistochemical study of the expression of a Mr 34,000 human epithelium-specific surface glycoprotein in normal and malignant tissues. Cancer Res. 1987;47:2883–2891
  83. Zorzos J, Zizi A, Bakiras A, et al. Expression of a cell surface antigen recognized by the monoclonal antibody AUA1 in bladder carcinoma: An immunohistochemical study. Eur Urol. 1995;28:251–254
  84. Tsubura A, Senzaki H, Sasaki M, et al. Immunohistochemical demonstration of breast-derived and/or carcinoma-associated glycoproteins in normal skin appendages and their tumors. J Cutan Pathol. 1992;19:73–79
  85. Litvinov SV, van Driel W, van Rhijn CM, et al. Expression of Ep-CAM in cervical squamous epithelia correlates with an increased proliferation and the disappearance of markers for terminal differentiation. Am J Pathol. 1996;148:865–875
  86. Bumol TF, Marder P, DeHerdt SV, et al. Characterization of the human tumor and normal tissue reactivity of the KS1/4 monoclonal antibody. Hybridoma. 1988;7:407–415
  87. Edwards DP, Grzyb KT, Dressler LG, et al. Monoclonal antibody identification and characterization of a Mr 43,000 membrane glycoprotein associated with human breast cancer. Cancer Res. 1986;46:1306–1317
  88. Zhang S, Zhang HS, Cordon-Cardo C, et al. Selection of tumor antigens as targets for immune attack using immunohistochemistry: Protein antigens. Clin Cancer Res. 1998;4:2669–2676
  89. Shetye J, Frodin JE, Christensson B, et al. Immunohistochemical monitoring of metastatic colorectal carcinoma in patients treated with monoclonal antibodies (MAb 17-1A). Cancer Immunol Immunother. 1988;27:154–162
  90. Shetye J, Christensson B, Rubio C, et al. The tumor-associated antigens BR55-2, GA73-3 and GICA 19–9 in normal and corresponding neoplastic human tissues, especially gastrointestinal tissues. Anticancer Res. 1989;9:395–404
  91. Ross AH, Herlyn D, Iliopoulos D, et al. Isolation and characterization of a carcinoma-associated antigen. Biochem Biophys Res Commun. 1986;135:297–303
  92. Ragnhammar P, Fagerberg J, Frodin JE, et al. Effect of monoclonal antibody 17-1A and GM-CSF in patients with advanced colorectal carcinoma–long-lasting, complete remissions can be induced. Int J Cancer. 1993;53:751–758
  93. Mellstedt H, Frodin JE, Masucci G, et al. The therapeutic use of monoclonal antibodies in colorectal carcinoma. Semin Oncol. 1991;18:462–477
  94. Weiner LM, Harvey E, Padavic-Shaller K, et al. Phase II multicenter evaluation of prolonged murine monoclonal antibody 17-1A therapy in pancreatic carcinoma. J Immunother. 1993;13:110–116
  95. Riethmuller G, Holz E, Schlimok G, et al. Monoclonal antibody therapy for resected Dukes C colorectal cancer: Seven-year outcome of a multicenter randomized trial. J Clin Oncol. 1998;16:1788–1794
  96. Roovers RC, Henderikx P, Helfrich W, et al. High-affinity recombinant phage antibodies to the pan-carcinoma marker epithelial glycoprotein-2 for tumour targeting. Br J Cancer. 1998;78:1407–1416
  97. Seligson DB, Pantuck AJ, Liu X, et al. Epithelial cell adhesion molecule (KSA) expression: Pathobiology and its role as an independent predictor of survival in renal cell carcinoma. Clin Cancer Res. 2004;10:2659–2669
  98. Zetter BR. Adhesion molecules in tumor metastasis. Semin Cancer Biol. 1993;4:219–229
  99. Shioi K, Komiya A, Hattori K, et al. Vascular cell adhesion molecule 1 predicts cancer-free survival in clear cell renal carcinoma patients. Clin Cancer Res. 2006;12:7339–7346
  100. Li F. Role of survivin and its splice variants in tumorigenesis. Br J Cancer. 2005;92:212–216
  101. Verhagen AM, Coulson EJ, Vaux DL. Inhibitor of apoptosis proteins and their relatives: IAPs and other BIRPs. Genome Biol. 2001;2:3009;(Review)
  102. Parker AS, Kosari F, Lohse CM, et al. High expression levels of survivin protein independently predict a poor outcome for patients who undergo surgery for clear cell renal cell carcinoma. Cancer. 2006;107:37–45
  103. Altieri DC. Survivin, versatile modulation of cell division and apoptosis in cancer. Oncogene. 2003;22:8581–8589
  104. Mizutani Y, Nakanishi H, Yamamoto K, et al. Down-regulation of Smac/DIABLO expression in renal cell carcinoma and its prognostic significance. J Clin Oncol. 2005;23:448–454
  105. Nagase H, Woessner JF. Matrix metalloproteinases. J Biol Chem. 1999;274:21491–21494
  106. Gomez DE, Alonso DF, Yoshiji H, et al. Tissue inhibitors of metalloproteinases: Structure, regulation, and biological functions. Eur J Cell Biol. 1997;74:111–122
  107. Murray GI, Duncan ME, O’Neil P, et al. Matrix metalloproteinase-1 is associated with poor prognosis in colorectal cancer. Nat Med. 1996;2:461–462
  108. Talvensaari-Mattila A, Paakko P, Hoyhtya M, et al. Matrix metalloproteinase-2 immunoreactive protein: A marker of aggressiveness in breast carcinoma. Cancer. 1998;83:1153–1162
  109. Bramhall SR, Neoptolemos JP, Stamp GW, et al. Imbalance of expression of matrix metalloproteinases (MMPs) and tissue inhibitors of the matrix metalloproteinases (TIMPs) in human pancreatic carcinoma. J Pathol. 1997;182:347–355
  110. Stearns M, Stearns ME. Evidence for increased activated metalloproteinase 2 (MMP-2a) expression associated with human prostate cancer progression. Oncol Res. 1996;8:69–75
  111. Kawano N, Osawa H, Ito T, et al. Expression of gelatinase A, tissue inhibitor of metalloproteinases-2, matrilysin, and trypsin(ogen) in lung neoplasms: An immunohistochemical study. Hum Pathol. 1997;28:613–622
  112. Kallakury BV, Karikehalli S, Haholu A, et al. Increased expression of matrix metalloproteinases 2 and 9 and tissue inhibitors of metalloproteinases 1 and 2 correlate with poor prognostic variables in renal cell carcinoma. Clin Cancer Res. 2001;7:3113–3119
  113. Miyata Y, Iwata T, Ohba K, et al. Expression of matrix metalloproteinase-7 on cancer cells and tissue endothelial cells in renal cell carcinoma: Prognostic implications and clinical significance for invasion and metastasis. Clin Cancer Res. 2006;12:6998–7003
  114. Baker AH, Ahonen M, Kahari VM. Potential applications of tissue inhibitor of metalloproteinase (TIMP) overexpression for cancer gene therapy. Adv Exp Med Biol. 2000;465:469–483
  115. Kugler A, Hemmerlein B, Thelen P, et al. Expression of metalloproteinase 2 and 9 and their inhibitors in renal cell carcinoma. J Urol. 1998;160:1914–1918
  116. Nemeth JA, Rafe A, Steiner M, et al. TIMP-2 growth-stimulatory activity: A concentration- and cell type-specific response in the presence of insulin. Exp Cell Res. 1996;224:110–115
  117. Murashige M, Miyahara M, Shiraishi N, et al. Enhanced expression of tissue inhibitors of metalloproteinases in human colorectal tumors. Jpn J Clin Oncol. 1996;26:303–309
  118. Ree AH, Florenes VA, Berg JP, et al. High levels of messenger RNAs for tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in primary breast carcinomas are associated with development of distant metastases. Clin Cancer Res. 1997;3:1623–1628
  119. Grignon DJ, Sakr W, Toth M, et al. High levels of tissue inhibitor of metalloproteinase-2 (TIMP-2) expression are associated with poor outcome in invasive bladder cancer. Cancer Res. 1996;56:1654–1659
  120. Andreasen PA, Egelund R, Petersen HH. The plasminogen activation system in tumor growth, invasion, and metastasis. Cell Mol Life Sci. 2000;57:25–40
  121. Yang JL, Seetoo D, Wang Y, et al. Urokinase-type plasminogen activator and its receptor in colorectal cancer: Independent prognostic factors of metastasis and cancer-specific survival and potential therapeutic targets. Int J Cancer. 2000;89:431–439
  122. Ohba K, Miyata Y, Kanda S, et al. Expression of urokinase-type plasminogen activator, urokinase-type plasminogen activator receptor and plasminogen activator inhibitors in patients with renal cell carcinoma: Correlation with tumor associated macrophage and prognosis. J Urol. 2005;174:461–465
  123. Hofmann R, Lehmer A, Buresch M, et al. Clinical relevance of urokinase plasminogen activator, its receptor, and its inhibitor in patients with renal cell carcinoma. Cancer. 1996;78:487–492
  124. Andreasen PA, Nielsen LS, Kristensen P, et al. Plasminogen activator inhibitor from human fibrosarcoma cells binds urokinase-type plasminogen activator, but not its proenzyme. J Biol Chem. 1986;261:7644–7651
  125. Rayman P, Wesa AK, Richmond AL, et al. Effect of renal cell carcinomas on the development of type 1 T-cell responses. Clin Cancer Res. 2004;10:6360S–6366S
  126. Uzzo RG, Rayman P, Kolenko V, et al. Mechanisms of apoptosis in T cells from patients with renal cell carcinoma. Clin Cancer Res. 1999;5:1219–1229
  127. Kudo D, Rayman P, Horton C, et al. Gangliosides expressed by the renal cell carcinoma cell line SK-RC-45 are involved in tumor-induced apoptosis of T cells. Cancer Res. 2003;63:1676–1683
  128. Latchman YE, Liang SC, Wu Y, et al. PD-L1-deficient mice show that PD-L1 on T cells, antigen-presenting cells, and host tissues negatively regulates T cells. Proc Natl Acad Sci USA. 2004;101:10691–10696
  129. Dong H, Strome SE, Salomao DR, et al. Tumor-associated B7–H1 promotes T-cell apoptosis: A potential mechanism of immune evasion. Nat Med. 2002;8:793–800
  130. Dong H, Zhu G, Tamada K, et al. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med. 1999;5:1365–1369
  131. Iwai Y, Ishida M, Tanaka Y, et al. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci USA. 2002;99:12293–12297
  132. Wintterle S, Schreiner B, Mitsdoerffer M, et al. Expression of the B7-related molecule B7-H1 by glioma cells: A potential mechanism of immune paralysis. Cancer Res. 2003;63:7462–7467
  133. Blank C, Brown I, Peterson AC, et al. PD-L1/B7H-1 inhibits the effector phase of tumor rejection by T cell receptor (TCR) transgenic CD8+ T cells. Cancer Res. 2004;64:1140–1145
  134. Thompson RH, Kuntz SM, Leibovich BC, et al. Tumor B7–H1 is associated with poor prognosis in renal cell carcinoma patients with long-term follow-up. Cancer Res. 2006;66:3381–3385
  135. Krambeck AE, Thompson RH, Dong H, et al. B7-H4 expression in renal cell carcinoma and tumor vasculature: Associations with cancer progression and survival. Proc Natl Acad Sci USA. 2006;103:10391–10396
  136. Ivan M, Kondo K, Yang H, et al. HIFα targeted for VHL-mediated destruction by proline hydroxylation: Implications for O2 sensing. Science. 2001;292:464–468
  137. Jaakkola P, Mole DR, Tian YM, et al. Targeting of HIF-α to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science. 2001;292:468–472
  138. Yu F, White SB, Zhao Q, et al. HIF-1α binding to VHL is regulated by stimulus-sensitive proline hydroxylation. Proc Natl Acad Sci USA. 2001;98:9630–9635
  139. Ivanov S, Liao SY, Ivanova A, et al. Expression of hypoxia-inducible cell-surface transmembrane carbonic anhydrases in human cancer. Am J Pathol. 2001;158:905–919
  140. Gnarra JR, Tory K, Weng Y, et al. Mutations of the VHL tumour suppressor gene in renal carcinoma. Nat Genet. 1994;7:85–90
  141. Yao M, Yoshida M, Kishida T, et al. VHL tumor suppressor gene alterations associated with good prognosis in sporadic clear-cell renal carcinoma. J Natl Cancer Inst. 2002;94:1569–1575
  142. Bui MH, Seligson D, Han KR, et al. Carbonic anhydrase IX is an independent predictor of survival in advanced renal clear cell carcinoma: Implications for prognosis and therapy. Clin Cancer Res. 2003;9:802–811
  143. Kim JH, Jung CW, Cho YH, et al. Somatic VHL alteration and its impact on prognosis in patients with clear cell renal cell carcinoma. Oncol Rep. 2005;13:859–864
  144. Lidgren A, Hedberg Y, Grankvist K, et al. The expression of hypoxia-inducible factor 1α is a favorable independent prognostic factor in renal cell carcinoma. Clin Cancer Res. 2005;11:1129–1135
  145. Lidgren A, Hedberg Y, Grankvist K, et al. Hypoxia-inducible factor 1α expression in renal cell carcinoma analyzed by tissue microarray. Eur Urol. 2006;50:1272–1277
  146. Raval RR, Lau KW, Tran MG, et al. Contrasting properties of hypoxia-inducible factor 1 (HIF-1) and HIF-2 in von Hippel-Lindau-associated renal cell carcinoma. Mol Cell Biol. 2005;25:5675–5686
  147. Carroll VA, Ashcroft M. Role of hypoxia-inducible factor (HIF)-1α versus HIF-2α in the regulation of HIF target genes in response to hypoxia, insulin-like growth factor-I, or loss of von Hippel-Lindau function: Implications for targeting the HIF pathway. Cancer Res. 2006;66:6264–6270
  148. Covello KL, Simon MC, Keith B. Targeted replacement of hypoxia-inducible factor-1α by a hypoxia-inducible factor-2α knock-in allele promotes tumor growth. Cancer Res. 2005;65:2277–2286
  149. Kondo K, Kim WY, Lechpammer M, et al. Inhibition of HIF2α is sufficient to suppress pVHL-defective tumor growth. PLoS Biol. 2003;1:E83
  150. Kondo K, Klco J, Nakamura E, et al. Inhibition of HIF is necessary for tumor suppression by the von Hippel-Lindau protein. Cancer Cell. 2002;1:237–246
  151. Kim HL, Seligson D, Liu X, et al. Molecular staging using protein expression profiling in metastatic clear cell renal carcinoma. J Urol. 2005;173:1496–1501
  152. Joo HJ, Oh DK, Kim YS, et al. Increased expression of caveolin-1 and microvessel density correlates with metastasis and poor prognosis in clear cell renal cell carcinoma. BJU Int. 2004;93:291–296
  153. Itoi T, Yamana K, Bilim V, et al. Impact of frequent Bcl-2 expression on better prognosis in renal cell carcinoma patients. Br J Cancer. 2004;90:200–205
  154. Campbell L, Gumbleton M, Griffiths DF. Caveolin-1 overexpression predicts poor disease-free survival of patients with clinically confined renal cell carcinoma. Br J Cancer. 2003;89:1909–1913
  155. Kurahashi T, Muramaki M, Yamanaka K, et al. Expression of the secreted form of clusterin protein in renal cell carcinoma as a predictor of disease extension. BJU Int. 2005;96:895–899
  156. Merseburger AS, Hennenlotter J, Simon P, et al. Membranous expression and prognostic implications of epidermal growth factor receptor protein in human renal cell cancer. Anticancer Res. 2005;25:1901–1907
  157. Parker A, Cheville JC, Lohse C, et al. Expression of insulin-like growth factor I receptor and survival in patients with clear cell renal cell carcinoma. J Urol. 2003;170:420–424
  158. Jacobsen J, Grankvist K, Rasmuson T, et al. Expression of vascular endothelial growth factor protein in human renal cell carcinoma. BJU Int. 2004;93:297–302
  159. Miyata Y, Koga S, Kanda S, et al. Expression of cyclooxygenase-2 in renal cell carcinoma: Correlation with tumor cell proliferation, apoptosis, angiogenesis, expression of matrix metalloproteinase-2, and survival. Clin Cancer Res. 2003;9:1741–1749
  160. Nakagawa Y, Tsumatani K, Kurumatani N, et al. Prognostic value of nm23 protein expression in renal cell carcinomas. Oncology. 1998;55:370–376
  161. Morell-Quadreny L, Clar-Blanch F, Fenollosa-Enterna B, et al. Proliferating cell nuclear antigen (PCNA) as a prognostic factor in renal cell carcinoma. Anticancer Res. 1998;18:677–682
  162. Soini Y, Kallio JP, Hirvikoski P, et al. Oxidative/nitrosative stress and peroxiredoxin 2 are associated with grade and prognosis of human renal carcinoma. APMIS. 2006;114:329–337
  163. Sandlund J, Hedberg Y, Bergh A, et al. Endoglin (CD105) expression in human renal cell carcinoma. BJU Int. 2006;97:706–710
  164. Kondo T, Nakazawa H, Ito F, et al. Favorable prognosis of renal cell carcinoma with increased expression of chemokines associated with a Th1-type immune response. Cancer Sci. 2006;97:780–786
  165. Matusan K, Dordevic G, Stipic D, et al. Osteopontin expression correlates with prognostic variables and survival in clear cell renal cell carcinoma. J Surg Oncol. 2006;94:325–331
  166. Takenawa J, Kaneko Y, Kishishita M, et al. Transcript levels of aquaporin 1 and carbonic anhydrase IV as predictive indicators for prognosis of renal cell carcinoma patients after nephrectomy. Int J Cancer. 1998;79:1–7
  167. Yao M, Tabuchi H, Nagashima Y, et al. Gene expression analysis of renal carcinoma: Adipose differentiation-related protein as a potential diagnostic and prognostic biomarker for clear-cell renal carcinoma. J Pathol. 2005;205:377–387
  168. Morita T, Matsuzaki A, Tokue A. Quantitative analysis of thymidine phosphorylase and dihydropyrimidine dehydrogenase in renal cell carcinoma. Oncology. 2003;65:125–131
  169. Paul R, Necknig U, Busch R, et al. Cadherin-6: A new prognostic marker for renal cell carcinoma. J Urol. 2004;171:97–101
  170. Ogushi T, Takahashi S, Takeuchi T, et al. Estrogen receptor-binding fragment-associated antigen 9 is a tumor-promoting and prognostic factor for renal cell carcinoma. Cancer Res. 2005;65:3700–3706
  171. Lucin K, Matusan K, Dordevic G, et al. Prognostic significance of CD44 molecule in renal cell carcinoma. Croat Med J. 2004;45:703–708
  172. Rioux-Leclercq N, Epstein JI, Bansard JY, et al. Clinical significance of cell proliferation, microvessel density, and CD44 adhesion molecule expression in renal cell carcinoma. Hum Pathol. 2001;32:1209–1215
  173. Ramp U, Caliskan E, Ebert T, et al. FHIT expression in clear cell renal carcinomas: Versatility of protein levels and correlation with survival. J Pathol. 2002;196:430–436
  174. Daniel L, Lechevallier E, Giorgi R, et al. CD44s and CD44v6 expression in localized T1-T2 conventional renal cell carcinomas. J Pathol. 2001;193:345–349
  175. Jiang Z, Chu PG, Woda BA, et al. Analysis of RNA-binding protein IMP3 to predict metastasis and prognosis of renal-cell carcinoma: A retrospective study. Lancet Oncol. 2006;7:556–564
  176. Li N, Tsuji M, Kanda K, et al. Analysis of CD44 isoform v10 expression and its prognostic value in renal cell carcinoma. BJU Int. 2000;85:514–518
  177. Petraki CD, Gregorakis AK, Vaslamatzis MM, et al. Prognostic implications of the immunohistochemical expression of human kallikreins 5, 6, 10 and 11 in renal cell carcinoma. Tumor Biol. 2006;27:1–7
  178. Aaltomaa S, Lipponen P, Karja V, et al. The expression and prognostic value of α-, β- and γ-catenins in renal cell carcinoma. Anticancer Res. 2004;24:2407–2413
  179. Langner C, Ratschek M, Rehak P, et al. CD10 is a diagnostic and prognostic marker in renal malignancies. Histopathology. 2004;45:460–467
  180. Shimazui T, Bringuier PP, van Berkel H, et al. Decreased expression of α-catenin is associated with poor prognosis of patients with localized renal cell carcinoma. Int J Cancer. 1997;74:523–528
  181. Horstmann M, Merseburger AS, von der Heyde E, et al. Correlation of bFGF expression in renal cell cancer with clinical and histopathological features by tissue microarray analysis and measurement of serum levels. J Cancer Res Clin Oncol. 2005;131:715–722
  182. Bamias A, Chorti M, Deliveliotis C, et al. Prognostic significance of CA 125, CD44, and epithelial membrane antigen in renal cell carcinoma. Urology. 2003;62:368–373
  183. Kraus S, Abel PD, Nachtmann C, et al. MUC1 mucin and trefoil factor 1 protein expression in renal cell carcinoma: Correlation with prognosis. Hum Pathol. 2002;33:60–67
  184. Went P, Dirnhofer S, Salvisberg T, et al. Expression of epithelial cell adhesion molecule (EpCam) in renal epithelial tumors. Am J Surg Pathol. 2005;29:83–88

PII: S1078-1439(07)00080-4

doi: 10.1016/j.urolonc.2007.03.028

Urologic Oncology: Seminars and Original Investigations
Volume 26, Issue 2 , Pages 113-124 , March 2008

Article Tools