Skip to main content

Molecular Diagnostics in Renal Cancer

  • Chapter
  • First Online:
Molecular Diagnostics in Cancer Patients

Abstract

Renal cancer is an aggressive and incurable disease with a worldwide prevalence that ranks it to be twelfth most common type of cancer. According to world cancer statistics, around 338,000 new kidney cancer incidences are diagnosed annually. Renal cancer is caused by various sporadic or familial mutations that lead to the accumulation of genomic aberrations enough to impair cell proliferation and differentiation. Epigenetic factors such as hypermethylation also adds up to the malignancy. Kidney heterogeneity makes it really tough to treat renal cancer since (a) different cells are affected in different types of renal cancer, and (b) diagnosis is very incidental and the symptoms appear only in the advance stages. Kidney cancer can be detected by conventional methods based on tumor morphology and tissue histology, while radical nephrectomy or more recently nephron-sparing surgery is the only treatment available in advance cancer stages. Evolvement of molecular techniques and integration in transcriptomics, proteomics and metabolomics, has lead to the quantification of a wide range of chemical fingerprints left behind by alterations caused by different types of renal cancer at earlier stages. These non-invasive biomarkers has the potential to detect renal cancer before they metastasize, improve cancer diagnosis, prognosis, and provide more personalized and targeted therapies in patient care. In this chapter, we have summarized the various molecular techniques and renal cancer biomarkers available to detect early stages with a possibility to have clinical implications in near future.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Ferlay J, Soerjomataram I, Mea E. GLOBOCAN 2012 v1.0, cancer incidence and mortality worldwide: IARC CancerBase No. 11. Lyon: International Agency for Research on Cancer; 2013. p. 1.0.

    Google Scholar 

  2. Bray F, Ren JS, Masuyer E, Ferlay J. Global estimates of cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer. 2013;132(5):1133–45.

    CAS  PubMed  Google Scholar 

  3. Linehan W, et al. Molecular diagnosis and therapy of kidney cancer. Annu Rev Med. 2010;61:329–43.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Pastore AL, et al. Serum and urine biomarkers for human renal cell carcinoma. Dis Mark. 2015;2015:251403.

    Google Scholar 

  5. Leppert JT, Pantuck AJ, Figlin RA, Belldegrun AS. The role of molecular markers in the staging of renal cell carcinoma. BJU Int. 2007;99(5b):1208–11.

    CAS  PubMed  Google Scholar 

  6. Audenet F, Yates D, Cancel-Tassin G, Cussenot O, Rouprêt M. Genetic pathways involved in carcinogenesis of clear cell renal cell carcinoma: genomics towards personalized medicine. BJU Int. 2012;109:1864–70.

    CAS  PubMed  Google Scholar 

  7. Daniel CR, et al. Large prospective investigation of meat intake, related mutagens, and risk of renal cell carcinoma. Am J Clin Nutr. 2012;95(1):155–62.

    CAS  PubMed  Google Scholar 

  8. T P, et al. Body size and risk of renal cell carcinoma in the European prospective investigation into cancer and nutrition (EPIC). Int J Cancer. 2006;118(3):728–38.

    Google Scholar 

  9. Xu Y, et al. The impact of smoking on survival in renal cell carcinoma: a systematic review and meta-analysis. Tumor Biol. 2014;35(7):6633–40.

    CAS  Google Scholar 

  10. Sanfilippo KM, et al. Hypertension and obesity and the risk of kidney cancer in 2 large cohorts of US men and women. Hypertension. 2014;63(5):934–41.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Hu J, et al. Renal cell carcinoma and occupational exposure to chemicals in Canada. Occup Med. 2002;52(3):157–64.

    CAS  Google Scholar 

  12. Muglia VF, Prando A. Renal cell carcinoma: histological classification and correlation with imaging findings. Radiol Bras. 2015;48(3):166–74.

    PubMed  PubMed Central  Google Scholar 

  13. Cairns P. Renal cell carcinoma. Cancer Biomark. 2011;9(1–6):461–73.

    PubMed Central  Google Scholar 

  14. Sachdeva K. Renal cell carcinoma staging; 2017. https://www.cancer.org/cancer/kidney-cancer/detection-diagnosis-staging/staging.html.

  15. Haase VH. The VHL/HIF oxygen-sensing pathway and its relevance to kidney disease. Kidney Int. 2006;69(8):1302–7.

    CAS  PubMed  Google Scholar 

  16. Organ S, Tsao M. An overview of the c-MET signaling pathway. Ther Adv Med Oncol. 2011;3(1 Suppl):S7–S19.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. L S, et al. Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas. Nat Genet. 1997;16(1):68–73.

    Google Scholar 

  18. Linehan WM, Srinivasan R, Schmidt LS. The genetic basis of kidney cancer: a metabolic disease. Nat Rev Urol. 2010;5:277.

    Google Scholar 

  19. Linehan WM, Walther MM, Zbar B. The genetic basis of cancer of the kidney. J Urol. 2003;170(6 Part 1):2163.

    CAS  PubMed  Google Scholar 

  20. Menko FH, et al. Hereditary leiomyomatosis and renal cell cancer (HLRCC). Renal cancer risk, surveillance and treatment. Fam Cancer. 2014;13(4):637–44.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Schneider M, et al. Early onset renal cell carcinoma in an adolescent girl with germline FLCN exon 5 deletion. Fam Cancer. 2018;17(1):135–9. Cite as(1):135–9.

    CAS  PubMed  Google Scholar 

  22. Pavlovich C, et al. Renal tumors in the Birt-Hogg-Dubé syndrome. Am J Surg Pathol. 2002;26(12):1542–52.

    PubMed  Google Scholar 

  23. Ramakrishnan S, Ellis L, Pili R. Histone modifications: implications in renal cell carcinoma. Epigenomics. 2013;5(4):453–62.

    CAS  PubMed  Google Scholar 

  24. Shenoy N, et al. Role of DNA methylation in renal cell carcinoma. J Hematol Oncol. 2015;8:88.

    PubMed  PubMed Central  Google Scholar 

  25. Tunuguntla HS, Jorda M. Diagnostic and prognostic molecular markers in renal cell carcinoma. J Urol. 2008;179(6):2096.

    CAS  PubMed  Google Scholar 

  26. Eichelberg C, Junker K, Ljungberg B, Moch H. Diagnostic and prognostic molecular markers for renal cell carcinoma: a critical appraisal of the current state of research and clinical applicability. Eur Urol. 2009;55(4):851–63.

    CAS  PubMed  Google Scholar 

  27. DI Carlo A. Evaluation of neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase-9 (MMP-9) and their complex MMP-9/NGAL in sera and urine of patients with kidney tumors. Oncol Lett. 2013;5(5):1677–81.

    Google Scholar 

  28. Won KH, et al. Human kidney injury molecule-1 is a tissue and urinary tumor marker of renal cell carcinoma. J Am Soc Nephrol. 2005;16(4):1126–34.

    Google Scholar 

  29. Bonventre J. Kidney injury molecule-1 (KIM-1): a urinary biomarker and much more. Nephrol Dial Transplant. 2009;24(11):3265–8.

    CAS  PubMed  Google Scholar 

  30. Jeremiah JM, Amy NL, Jingqin L, Evan DK. Urinary biomarkers for the early diagnosis of kidney cancer. Mayo Clin Proc. 2010;85(5):413–21.

    Google Scholar 

  31. Rajandram R, et al. Tumour necrosis factor receptor-associated factor-1 (TRAF-1) expression is increased in renal cell carcinoma patient serum but decreased in cancer tissue compared with normal: potential biomarker significance. Pathology. 2014;46(6):518–22.

    CAS  PubMed  Google Scholar 

  32. Bennett NC, et al. Patient samples of renal cell carcinoma show reduced expression of TRAF1 compared with normal kidney and functional studies in vitro indicate TRAF1 promotes apoptosis: potential for targeted therapy. Pathology. 2012;44(5):453–9.

    PubMed  Google Scholar 

  33. Hofbauer S, et al. Pretherapeutic gamma-glutamyltransferase is an independent prognostic factor for patients with renal cell carcinoma. Br J Cancer. 2014;111(8):1526–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Ramp U, et al. Apoptosis induction in renal cell carcinoma by TRAIL and γ-radiation is impaired by deficient caspase-9 cleavage. Br J Cancer. 2003;88(11):1800–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Déjosez M, et al. Sensitivity to TRAIL/APO-2L-mediated apoptosis in human renal cell carcinomas and its enhancement by topotecan. Cell Death Differ. 2000;7(11):1127–36.

    PubMed  Google Scholar 

  36. I Y, et al. Serum M65 as a biomarker for metastatic renal cell carcinoma. Clin Genitourin Cancer. 2013;11(3):290–6.

    Google Scholar 

  37. Frew IJ, Moch H. A clearer view of the molecular complexity of clear cell renal cell carcinoma. Annu Rev Pathol Mech Dis. 2015;10(1):263–89.

    CAS  Google Scholar 

  38. Tanaka T, Kitamura H, Torigoe T, et al. Autoantibody against hypoxia-inducible factor prolyl hydroxylase-3 is a potential serological marker for renal cell carcinoma. J Cancer Res Clin Oncol. 2011;137(5):789–94.

    CAS  PubMed  Google Scholar 

  39. Takacova M, et al. Carbonic anhydrase IX is a clinically significant tissue and serum biomarker associated with renal cell carcinoma. Oncol Lett. 2013;5(1):191–7.

    CAS  PubMed  Google Scholar 

  40. Silva D, et al. Serum tissue factor as a biomarker for renal clear cell carcinoma. Int Braz J Urol. 2018;44(1):38–44.

    PubMed  PubMed Central  Google Scholar 

  41. Tan W, et al. Role of inflammatory related gene expression in clear cell renal cell carcinoma development and clinical outcomes. J Urol. 2011;186(5):2071–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Iqbal MA, Akhtar M, Al Dayel F, Ulmer C, Paterson MC. Use of fish analysis for diagnosis of renal cell carcinoma subtypes. Ann Saudi Med. 1999;19(6):495–500.

    CAS  PubMed  Google Scholar 

  43. Kim S, et al. Usefulness of a break-apart FISH assay in the diagnosis of Xp11.2 translocation renal cell carcinoma. Virchows Arch. 2011;459(3):299–306.

    CAS  PubMed  Google Scholar 

  44. Pradhan D, et al. Validation and utilization of a TFE3 break-apart FISH assay for Xp11.2 translocation renal cell carcinoma and alveolar soft part sarcoma. Diagn Pathol. 2015;10(1):179.

    PubMed  PubMed Central  Google Scholar 

  45. Pflueger D, et al. Identification of molecular tumor markers in renal cell carcinomas with TFE3 protein expression by RNA sequencing. Neoplasia. 2013;15(11):1231–40.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Hahn AW, et al. Correlation of genomic alterations assessed by next-generation sequencing (NGS) of tumor tissue DNA and circulating tumor DNA (ctDNA) in metastatic renal cell carcinoma (mRCC): potential clinical implications. Oncotarget. 2017;8(20):33614–20.

    PubMed  PubMed Central  Google Scholar 

  47. Di Napoli A, Signoretti S. Tissue biomarkers in renal cell carcinoma: issues and solutions. Cancer. 2009;115(10 Suppl):2290–7.

    PubMed  Google Scholar 

  48. Barr ML, et al. PAX-8 expression in renal tumours and distant sites: a useful marker of primary and metastatic renal cell carcinoma? J Clin Pathol. 2014;68(1):12–7.

    PubMed  PubMed Central  Google Scholar 

  49. Knoepp S, Kunju LP, Roh MH. Utility of PAX8 and PAX2 immunohistochemistry in the identification of renal cell carcinoma in diagnostic cytology. Diagn Cytopathol. 2012;40(8):667–72.

    PubMed  Google Scholar 

  50. Miettinen M, Lasota J. KIT (CD117): a review on expression in normal and neoplastic tissues, and mutations and their clinicopathologic correlation. Appl Immunohistochem Mol Morphol. 2005;13(3):205–20.

    CAS  PubMed  Google Scholar 

  51. Ahmed EA, Youssif ME. Immunohistochemical study of c-KIT (CD117) expression in renal cell carcinoma. J Egypt Natl Canc Inst. 2009;21(2):121–32.

    PubMed  Google Scholar 

  52. Martignoni G, et al. Validation of 34betaE12 immunoexpression in clear cell papillary renal cell carcinoma as a sensitive biomarker. Pathology. 2017;49(1):10–8.

    CAS  PubMed  Google Scholar 

  53. Farber N, et al. Renal cell carcinoma: the search for a reliable biomarker. Transl Cancer Res. 2017;6(3):620–32.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Slade L, Pulinilkunnil T. The MiTF/TFE family of transcription factors: master regulators of organelle signaling, metabolism, and stress adaptation. Mol Cancer Res. 2017 15(12):1637–43.

    Google Scholar 

  55. Alshenawy HA. Immunohistochemical panel for differentiating renal cell carcinoma with clear and papillary features. Pathol Oncol Res. 2015;21(4):893–9.

    CAS  PubMed  Google Scholar 

  56. Lee HJ, et al. Combination of immunohistochemistry, FISH and RT-PCR shows high incidence of Xp11 translocation RCC: comparison of three different diagnostic methods. Oncotarget. 2017;8(19):30756–65.

    PubMed  PubMed Central  Google Scholar 

  57. Kim K, et al. Urine metabolomics analysis for kidney cancer detection and biomarker discovery. Mol Cell Proteomics. 2009;8(3):558–70.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Kind T, Tolstikov V, Fiehn O, Weiss R. A comprehensive urinary metabolomic approach for identifying kidney cancer. Anal Biochem. 2007;363(2):185–95.

    CAS  PubMed  Google Scholar 

  59. Rogers M, et al. Proteomic profiling of urinary proteins in renal cancer by surface enhanced laser desorption ionization and neural-network analysis. Cancer Res. 2003;63(20):6971–83.

    CAS  PubMed  Google Scholar 

  60. Fischer K, Theil G, Hoda R, Fornara P. Serum amyloid a: a biomarker for renal cancer. Anticancer Res. 2012;32(5):1801–4.

    CAS  PubMed  Google Scholar 

  61. Wulfken L, et al. MicroRNAs in renal cell carcinoma: diagnostic implications of serum miR-1233 levels. PLoS One. 2011;6(9):e25787.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Wang C, et al. A panel of five serum miRNAs as a potential diagnostic tool for early-stage renal cell carcinoma. Sci Rep. 2015;5(1):7610.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Li M, et al. MicroRNAs in renal cell carcinoma: a systematic review of clinical implications (review). Oncol Rep. 2015;33(4):1571–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Li M, Wang Y, Cheng L, Niu W, Zhao G, Raju JK, et al. Long non-coding RNAs in renal cell carcinoma: a systematic review and clinical implications. Oncotarget. 2017;8(29):48424–35.

    PubMed  PubMed Central  Google Scholar 

  65. Yu G, et al. LncRNAs expression signatures of renal clear cell carcinoma revealed by microarray. PLoS One. 2012;7(8):e42377.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Ellinger J, et al. The long non-coding RNA lnc-ZNF180–2 is a prognostic biomarker in patients with clear cell renal cell carcinoma. Am J Cancer Res. 2015;5(9):2799–807.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Ball MW, et al. Circulating tumor DNA as a marker of therapeutic response in patients with renal cell carcinoma: a pilot study. Clin Genitourin Cancer. 2016;14(5):e515–20.

    PubMed  PubMed Central  Google Scholar 

  68. Cohen RJ. Pathology of clear cell renal cell carcinoma; 2016. https://emedicine.medscape.com/article/1612043-overview.

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Sanganeria, B.S., Misra, R., Shukla, K.K. (2019). Molecular Diagnostics in Renal Cancer. In: Shukla, K., Sharma, P., Misra, S. (eds) Molecular Diagnostics in Cancer Patients. Springer, Singapore. https://doi.org/10.1007/978-981-13-5877-7_13

Download citation

  • DOI: https://doi.org/10.1007/978-981-13-5877-7_13

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-13-5876-0

  • Online ISBN: 978-981-13-5877-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics