Diagnostic and Prognostic Molecular Markers for Renal Cell Carcinoma: A Critical Appraisal of the Current State of Research and Clinical Applicability

European Urology

Volumn 55, Issue 4, 2009, Pages 851-863

  Eichelberg, Christian ^a   Junker, Kerstin ^b   Ljungberg, Börje ^c   Moch, Holger ^d  

^a UNIVERSITY MEDICAL CENTER HAMBURG EPPENDORF   (Germany)

^b FRIEDRICH SCHILLER UNIVERSITY JENA   (Germany)

^c UMEÅ UNIVERSITY   (Sweden)

^d UNIVERSITY HOSPITAL ZURICH   (Switzerland)

Author keywords

Biopsy; Blood; Molecular marker; Prognosis; Renal cell carcinoma; Therapy response; Tissue; Urine

Indexed keywords

MOLECULAR MARKER;

CANCER DIAGNOSIS; CANCER SCREENING; CANCER SURVIVAL; CLINICAL TRIAL; HUMAN; IMMUNOHISTOCHEMISTRY; KIDNEY CARCINOMA; PRIORITY JOURNAL; PROGNOSIS; REVIEW; RISK FACTOR; TUMOR BIOPSY; TUMOR GROWTH;

BIOLOGICAL MARKERS; BIOMEDICAL RESEARCH; CARCINOMA, RENAL CELL; HUMANS; KIDNEY NEOPLASMS; PROGNOSIS;

EID: 60249098046     PISSN: 03022838     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.eururo.2009.01.003     Document Type: Review

References (94)

1. National Cancer Institute. Surveillance, Epidemiology, and End Results (SEER). http://www.seer.cancer.gov.
2. Ljungberg B., Hanbury D.C., Kuczyk M.A., et al. Renal cell carcinoma guideline. Eur Urol 51 (2007) 1502-1510
3. Hollingsworth J.M., Miller D.C., Daignault S., and Hollenbeck B.K. Rising incidence of small renal masses: a need to reassess treatment effect. J Natl Cancer Inst 98 (2006) 1331-1334
4. In: Sobin L.H., and Wittekind C.H. (Eds). International Union Against Cancer (UICC) TNM Classification of Malignant Tumours. 6th ed. (2002), Wiley-Liss, New York, NY 193-195
5. Margulis V., Tamboli P., Matin S.F., Meisner M., Swanson D.A., and Wood C.G. Redefining pT3 renal cell carcinoma in the modern era. Cancer 109 (2007) 2439-2444
6. Kim H.L., Seligson D., Liu X., et al. Using protein expressions to predict survival in clear cell renal carcinoma. Clin Cancer Res 10 (2004) 5464-5471
7. Ficarra V., Novara G., Iafrate M., et al. Proposal for reclassification of the TNM staging system in patients with locally advanced (pT3-4) renal cell carcinoma according to the cancer-related outcome. Eur Urol 51 (2007) 722-731 discussion 729-31
8. Thompson R.H., Cheville J.C., Lohse C.M., et al. Reclassification of patients with pT3 and pT4 renal cell carcinoma improves prognostic accuracy. Cancer 104 (2005) 53-60
9. Hupertan V., Roupret M., Poisson J.F., et al. Low predictive accuracy of the Kattan postoperative nomogram for renal cell carcinoma recurrence in a population of French patients. Cancer 107 (2006) 2604-2608
10. Galfano A., Novara G., Iafrate M., et al. Mathematical models for prognostic prediction in patients with renal cell carcinoma. Urol Int 80 (2008) 113-123
11. Cindolo L., Patard J.J., Chiodini P., et al. Comparison of predictive accuracy of four prognostic models for nonmetastatic renal cell carcinoma after nephrectomy: a multicenter European study. Cancer 104 (2005) 1362-1371
12. Ross J.S., Fletcher J.A., Bloom K.J., et al. HER-2/neu testing in breast cancer. Am J Clin Pathol 120 Suppl (2003) S53-71
13. Struckmann K., Mertz K., Steu S., et al. pVHL co-ordinately regulates CXCR4/CXCL12 and MMP2/MMP9 expression in human clear-cell renal cell carcinoma. J Pathol 214 (2008) 464-471
14. Frew I.J., and Krek W. pVHL: a multipurpose adaptor protein. Sci Signal 1 (2008) pe30
15. 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 94 (2002) 1569-1575
16. Schraml P., Struckmann K., Hatz F., et al. VHL mutations and their correlation with tumour cell proliferation, microvessel density, and patient prognosis in clear cell renal cell carcinoma. J Pathol 196 (2002) 186-193
17. Rini B.I., Jaeger E., Weinberg V., et al. Clinical response to therapy targeted at vascular endothelial growth factor in metastatic renal cell carcinoma: impact of patient characteristics and Von Hippel-Lindau gene status. BJU Int 98 (2006) 756-762
18. Wiesener M.S., Munchenhagen P.M., Berger I., et al. Constitutive activation of hypoxia-inducible genes related to overexpression of hypoxia-inducible factor-1alpha in clear cell renal carcinomas. Cancer Res 61 (2001) 5215-5222
19. Lidgren A., Hedberg Y., Grankvist K., Rasmuson T., Vasko J., and Ljungberg B. The expression of hypoxia-inducible factor 1alpha is a favorable independent prognostic factor in renal cell carcinoma. Clin Cancer Res 11 (2005) 1129-1135
20. Lidgren A., Hedberg Y., Grankvist K., Rasmuson T., Bergh A., and Ljungberg B. Hypoxia-inducible factor 1α expression in renal cell carcinoma analyzed by tissue microarray. Eur Urol 50 (2006) 1272-1277
21. Klatte T., Seligson D.B., Riggs S.B., et al. Hypoxia-inducible factor 1 alpha in clear cell renal cell carcinoma. Clin Cancer Res 13 (2007) 7388-7393
22. An W.G., Kanekal M., Simon M.C., Maltepe E., Blagosklonny M.V., and Neckers L.M. Stabilization of wild-type p53 by hypoxia-inducible factor 1alpha. Nature 392 (1998) 405-408
23. Na X., Wu G., Ryan C.K., Schoen S.R., di'Santagnese P.A., and Messing E.M. Overproduction of vascular endothelial growth factor related to von Hippel-Lindau tumor suppressor gene mutations and hypoxia-inducible factor-1 alpha expression in renal cell carcinomas. J Urol 170 (2003) 588-592
24. Yildiz E., Gokce G., Kilicarslan H., Ayan S., Goze O.F., and Gultekin E.Y. Prognostic value of the expression of Ki-67, CD44 and vascular endothelial growth factor, and microvessel invasion, in renal cell carcinoma. BJU Int 93 (2004) 1087-1093
25. Jacobsen J., Grankvist K., Rasmuson T., Bergh A., Landberg G., and Ljungberg B. Expression of vascular endothelial growth factor protein in human renal cell carcinoma. BJU Int 93 (2004) 297-302
26. Paradis V., Lagha N.B., Zeimoura L., et al. Expression of vascular endothelial growth factor in renal cell carcinomas. Virchows Arch 436 (2000) 351-356
27. Yildiz E., Ayan S., Goze F., Gokce G., and Gultekin E.Y. Relation of microvessel density with microvascular invasion, metastasis and prognosis in renal cell carcinoma. BJU Int 101 (2008) 758-764
28. Murphy D.A., Makonnen S., Lassoued W., Feldman M.D., Carter C., and Lee W.M. Inhibition of tumor endothelial ERK activation, angiogenesis, and tumor growth by sorafenib (BAY43-9006). Am J Pathol 169 (2006) 1875-1885
29. Bukowski R., Heng D., Eisen T., et al. Sorafenib in advanced renal cell carcinoma (RCC): survival and biomarker results from a phase III trial. Eur Urol Suppl 7 (2008) 245
30. Oosterwijk E., Ruiter D.J., Hoedemaeker P.J., et al. Monoclonal antibody G 250 recognizes a determinant present in renal-cell carcinoma and absent from normal kidney. Int J Cancer 38 (1986) 489-494
31. Pastorek J., Pastorekova S., Callebaut I., et al. Cloning and characterization of MN, a human tumor-associated protein with a domain homologous to carbonic anhydrase and a putative helix-loop-helix DNA binding segment. Oncogene 9 (1994) 2877-2888
32. Grabmaier K.A., de Weijert M.C., Verhaegh G.W., Schalken J.A., and Oosterwijk E. Strict regulation of CAIX(G250/MN) by HIF-1alpha in clear cell renal cell carcinoma. Oncogene 23 (2004) 5624-5631
33. Liao S.Y., Aurelio O.N., Jan K., Zavada J., and Stanbridge E.J. Identification of the MN/CA9 protein as a reliable diagnostic biomarker of clear cell carcinoma of the kidney. Cancer Res 57 (1997) 2827-2831
34. Bui M.H., Seligson D., Han K.R., 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 9 (2003) 802-811
35. Tennstedt P., Schneider P., Oosterwijk E., et al. Investigation of Ca9 expression in pulmonal metastatic lesions from patients with clear cell renal cell carcinoma. J Urol 179 (2008) 136
36. Bui M.H., 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 171 (2004) 2461-2466
37. Leibovich B.C., Sheinin Y., Lohse C.M., et al. Carbonic anhydrase IX is not an independent predictor of outcome for patients with clear cell renal cell carcinoma. J Clin Oncol 25 (2007) 4757-4764
38. Atkins M., Regan M., McDermott D., et al. Carbonic anhydrase IX expression predicts outcome of interleukin 2 therapy for renal cancer. Clin Cancer Res 11 (2005) 3714-3721
39. Oosterwijk E., Debruyne F.M., and Schalken J.A. The use of monoclonal antibody G250 in the therapy of renal-cell carcinoma. Semin Oncol 22 (1995) 34-41
40. Hudes G., Carducci M., Tomczak P., et al. A phase 3, randomized, 3-arm study of temsirolimus (TEMSR) or interferon-alpha (IFN) or the combination of TEMSR + IFN in the treatment of first-line, poor-risk patients with advanced renal cell carcinoma (adv RCC) [abstract]. J Clin Oncol 24 Suppl (2006) LBA4
41. Motzer R.J., Escudier B., Oudard S., et al. RAD001 vs placebo in patients with metastatic renal cell carcinoma (RCC) after progression on VEGFr-TKI therapy: results from a randomized, double-blind, multicenter phase-III study [abstract]. J Clin Oncol 26 Suppl (2008) LBA5026
42. Youssif T., Tanguay S., Alam-Fahmy M., Koumakpayi I., and Sircar K. Expression of PI3K/AKT/mTOR pathway in renal cell carcinoma metastases: correlation with pathologic findings and survival. J Urol 179 (2008) 210
43. Pantuck A., Seligson D.B., Klatte T., et al. Prognostic relevance of the mTOR pathway in renal cell carcinoma. Cancer 109 (2007) 2257-2267
44. Cho D., Signoretti S., Dabora S., et al. Potential histologic and molecular predictors of response to temsirolimus in patients with advanced renal cell carcinoma. Clin Genitourin Cancer 5 (2007) 379-385
45. Velickovic M., Delahunt B., McIver B., and Grebe S.K. Intragenic PTEN/MMAC1 loss of heterozygosity in conventional (clear-cell) renal cell carcinoma is associated with poor patient prognosis. Mod Pathol 15 (2002) 479-485
46. Sejima T., and Miyagawa I. Expression of Bcl-2, p53 oncoprotein, and proliferating cell nuclear antigen in renal cell carcinoma. Eur Urol 35 (1999) 242-248
47. Zigeuner R., Ratschek M., Rehak P., Schips L., and Langner C. Value of p53 as a prognostic marker in histologic subtypes of renal cell carcinoma: a systematic analysis of primary and metastatic tumor tissue. Urology 63 (2004) 651-655
48. Mombini H., Givi M., and Rashidi I. Relationship between expression of p53 protein and tumor subtype and grade in renal cell carcinoma. J Urol 3 (2006) 79-81
49. 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 55 (2000) 501-505
50. 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 173 (2005) 725-728
51. Klatte T., Seligson D.B., Leppert J.T., et al. The chemokine receptor CXCR3 is an independent prognostic factor in patients with localized clear cell renal cell carcinoma. J Urol 179 Suppl (2008) 61-66
52. Staller P., Sulitkova J., Lisztwan J., Moch H., Oakeley E.J., and Krek W. Chemokine receptor CXCR4 downregulated by von Hippel-Lindau tumour suppressor pVHL. Nature 425 (2003) 307-311
53. Chawla R., Kramer M., Siva H., Tunuguntla G.R., Jorda M., and Lokeshwar B.L. Is CXCR-4 a new prognostic and metastatic marker in renal cell carcinoma?. J Urol 179 Suppl (2008) 139
54. Kallakury B.V., Karikehalli S., Haholu A., Sheehan C.E., Azumi N., and Ross J.S. 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 7 (2001) 3113-3119
55. Kugler A., Hemmerlein B., Thelen P., Kallerhoff M., Radzun H.J., and Ringert R.H. Expression of metalloproteinase 2 and 9 and their inhibitors in renal cell carcinoma. J Urol 160 (1998) 1914-1918
56. Kawata N., Nagane Y., Igarashi T., et al. Strong significant correlation between MMP-9 and systemic symptoms in patients with localized renal cell carcinoma. Urology 68 (2006) 523-527
57. Hoffmann N.E., Sheinin Y., Lohse C.M., et al. External validation of IMP3 expression as an independent prognostic marker for metastatic progression and death for patients with clear cell renal cell carcinoma. Cancer 112 (2008) 1471-1479
58. Jiang Z., Chu P.G., Woda B.A., et al. Analysis of RNA-binding protein IMP3 to predict metastasis and prognosis of renal-cell carcinoma: a retrospective study. Lancet Oncol 7 (2006) 556-564
59. Jiang Z., Lohse C.M., Chu P.G., et al. Oncofetal protein IMP3: a novel molecular marker that predicts metastasis of papillary and chromophobe renal cell carcinomas. Cancer 112 (2008) 2676-2682
60. Seligson D.B., Pantuck A.J., 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 10 (2004) 2659-2669
61. Went P., Dirnhofer S., Salvisberg T., et al. Expression of epithelial cell adhesion molecule (EpCam) in renal epithelial tumors. Am J Surg Pathol 29 (2005) 83-88
62. Moch H., Schraml P., Bubendorf L., et al. High-throughput tissue microarray analysis to evaluate genes uncovered by cDNA microarray screening in renal cell carcinoma. Am J Pathol 154 (1999) 981-986
63. Zigeuner R., Droschl N., Tauber V., Rehak P., and Langner C. Biologic significance of fascin expression in clear cell renal cell carcinoma: systematic analysis of primary and metastatic tumor tissues using a tissue microarray technique. Urology 68 (2006) 518-522
64. Wagener N., Crnkovic-Mertens I., Vetter C., et al. Expression of inhibitor of apoptosis protein livin in renal cell carcinoma and non-tumorous adult kidney. Br J Cancer 97 (2007) 1271-1276
65. Kempkensteffen C., Hinz S., Christoph F., et al. Expression of the apoptosis inhibitor livin in renal cell carcinomas: correlations with pathology and outcome. Tumour Biol 28 (2007) 132-138
66. Kosari F., Parker A.S., Kube D.M., et al. Clear cell renal cell carcinoma: gene expression analyses identify a potential signature for tumor aggressiveness. Clin Cancer Res 11 (2005) 5128-5139
67. Byun S.S., Yeo W.G., Lee S.E., and Lee E. Expression of survivin in renal cell carcinomas: association with pathologic features and clinical outcome. Urology 69 (2007) 34-37
68. Parker A.S., Kosari F., Lohse C.M., 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 107 (2006) 37-45
69. Li G., Cuilleron M., Cottier M., et al. The use of MN/CA9 gene expression in identifying malignant solid renal tumors. Eur Urol 49 (2006) 401-405
70. Junker K., Hindermann W., von Eggeling F., Diegmann J., Haessler K., and Schubert J. CD70: a new tumor specific biomarker for renal cell carcinoma. J Urol 173 (2005) 2150-2153
71. Perret A.G., Clemencon A., Li G., Tostain J., and Peoc'h M. Differential expression of prognostic markers in histological subtypes of papillary renal cell carcinoma. BJU Int 102 (2008) 183-187
72. Yamazaki K., Sakamoto M., Ohta T., Kanai Y., Ohki M., and Hirohashi S. Overexpression of KIT in chromophobe renal cell carcinoma. Oncogene 22 (2003) 847-852
73. Pan C.C., Chen P.C., and Chiang H. Overexpression of KIT (CD117) in chromophobe renal cell carcinoma and renal oncocytoma. Am J Clin Pathol 121 (2004) 878-883
74. Kruger S., Sotlar K., Kausch I., and Horny H.P. Expression of KIT (CD117) in renal cell carcinoma and renal oncocytoma. Oncology 68 (2005) 269-275
75. Kauffman E.C., Barocas D.A., Yang X.J., Liu H., Scherr D.S., and Tu J.J. KAI1 is a novel biomarker for chromophobe renal cell carcinoma. J Urol 179 (2008) 134
76. Klatte T., Nagesh Rao P., Martino M.D., et al. Gender specific cytogenetic signatures can distinguish between oncocytoma and chromophobe renal cell carcinoma. J Urol 179 Suppl (2008) 168
77. McKiernan J.M., Buttyan R., Bander N.H., et al. The detection of renal carcinoma cells in the peripheral blood with an enhanced reverse transcriptase-polymerase chain reaction assay for MN/CA9. Cancer 86 (1999) 492-497
78. Gilbert S.M., Whitson J.M., Mansukhani M., et al. Detection of carbonic anhydrase-9 gene expression in peripheral blood cells predicts risk of disease recurrence in patients with renal cortical tumors. Urology 67 (2006) 942-945
79. Jacobsen J., Rasmuson T., Grankvist K., and Ljungberg B. Vascular endothelial growth factor as prognostic factor in renal cell carcinoma. J Urol 163 (2000) 343-347
80. Rioux-Leclercq N., Fergelot P., Zerrouki S., et al. Plasma level and tissue expression of vascular endothelial growth factor in renal cell carcinoma: a prospective study of 50 cases. Hum Pathol 38 (2007) 1489-1495
81. Klatte T., Bohm M., Nelius T., Filleur S., Reiher F., and Allhoff E.P. Evaluation of peri-operative peripheral and renal venous levels of pro- and anti-angiogenic factors and their relevance in patients with renal cell carcinoma. BJU Int 100 (2007) 209-214
82. Negrier S., Chabaud S., Escudier B., et al. Serum level of vascular endothelial growth factor (VEGF) as an independent prognostic factor in metastatic renal cell carcinoma (MRCC) [abstract]. J Clin Oncol 25 Suppl (2007) 5044
83. Escudier B., Ravaud A., Négrier S., et al. Update on AVOREN trial in metastatic renal cell carcinoma (mRCC): efficacy and safety in subgroups of patients (pts) and pharmacokinetic (PK) analysis [abstract]. J Clin Oncol 26 Suppl (2008) 5025
84. Ramankulov A., Lein M., Johannsen M., et al. Serum amyloid A as indicator of distant metastases but not as early tumor marker in patients with renal cell carcinoma. Cancer Lett 28 (2008) 269 85-92
85. Junker K., von Eggeling F., Muller J., Steiner T., and Schubert J. Identification of biomarkers and therapeutic targets for renal cell cancer using ProteinChip technology [in German]. Urologe A 45 (2006) 305-306 308, 310-2
86. Rasmuson T., Grankvist K., Jacobsen J., Olsson T., and Ljungberg B. Serum insulin-like growth factor-1 is an independent predictor of prognosis in patients with renal cell carcinoma. Acta Oncol 43 (2004) 744-748
87. Kaya K., Ayan S., Gokce G., Kilicarslan H., Yildiz E., and Gultekin E.Y. Urinary nuclear matrix protein 22 for diagnosis of renal cell carcinoma. Scand J Urol Nephrol 39 (2005) 25-29
88. Ozer G., Altinel M., Kocak B., Yazicioglu A., and Gonenc F. Value of urinary NMP-22 in patients with renal cell carcinoma. Urology 60 (2002) 593-597
89. Huang S., Rhee E., Patel H., Park E., and Kaswick J. Urinary NMP22 and renal cell carcinoma. Urology 55 (2000) 227-230
90. Rogers M.A., Clarke P., Noble J., et al. Proteomic profiling of urinary proteins in renal cancer by surface enhanced laser desorption ionization and neural-network analysis: identification of key issues affecting potential clinical utility. Cancer Res 63 (2003) 6971-6983
91. Holcakova J., Hernychova L., Bouchal P., et al. Identification of alphaB-crystallin, a biomarker of renal cell carcinoma by SELDI-TOF-MS. Int J Biol Markers 23 (2008) 48-53
92. Wu D.L., Zhang W.H., Wang W.J., Jing S.B., and Xu Y.M. Proteomic evaluation of urine from renal cell carcinoma using SELDI-TOF-MS and tree analysis pattern. Technol Cancer Res Treat 7 (2008) 155-160
93. Teratani T., Domoto T., Kuriki K., et al. Detection of transcript for brain-type fatty acid-binding protein in tumor and urine of patients with renal cell carcinoma. Urology 69 (2007) 236-240
94. Moch H., Gasser T., Amin M.B., Torhorst J., Sauter G., and Mihatsch M.J. Prognostic utility of the recently recommended histologic classification and revised TNM staging system of renal cell carcinoma: a Swiss experience with 588 tumors. Cancer 89 (2000) 604-614