Advertisement

Molecular Analysis in Pediatric Renal Tumors

  • Lawrence JenningsEmail author
Chapter
  • 816 Downloads
Part of the Molecular and Translational Medicine book series (MOLEMED)

Abstract

Although the incidence of pediatric cancers has increased steadily over the last 35 years, the incidence of pediatric kidney tumors has not changed in the same time period. Pediatric kidney tumors represent approximately 5% of cancer diagnoses among children and adolescents below the age of 20 (http://seer.cancer.gov/, Fig. 10.1). However, the incidence is age dependent so that malignant kidney tumors account for 9.7% of the total among children younger than 5 years of age, 5.4% in children 5–9 years of age, 1.1% in children 10–14 years of age, and 0.6% in adolescents 15–19 years of age. Of the approximately 550 children and adolescents diagnosed with renal tumors each year, approximately 500 are Wilms tumor (WT). The remaining includes variants of renal cell carcinoma (RCC), clear cell sarcoma of the kidney, rhabdoid tumor of the kidney, congenital mesoblastic nephroma (CMN), as well as other rare tumors (Histopathology 54:516–528, 2009). Because the incidence of WT and other pediatric renal tumors is very much agedependent, age at diagnosis perhaps provides the best clinical clue to the diagnosis. For example, some tumors occur almost entirely in infancy (e.g., CMN) whereas others occur almost exclusively in adolescence (e.g., RCC). Indeed, RCC accounts for about 5% of pediatric renal tumors but comprises the majority of tumors by late adolescence (Cancer Incidence and Survival among Children and Adolescents: United States SEER Program 1975–1995, National Cancer Institute, SEER Program, 1999) (Fig. 10.2).

Keywords

Kidney Renal Tumor Molecular Genetic Diagnosis Childhood Pediatric 

References

  1. 1.
    Sebire NJ, Vujanic GM. Paediatric renal tumours: recent developments, new entities and pathological features. Histopathology. 2009;54:516–28.PubMedCrossRefGoogle Scholar
  2. 2.
    Bernstein L, Linet M, Smith MA, Olshan AF. Renal tumors. In: Ries LAG, Smith M, Gurney JG, Linet M, Tamra T, Young JL, Bunin GR, editors. Cancer incidence and survival among children and adolescents: United States SEER Program 1975–1995 National Cancer Institute, SEER Program. Bethesda, MD: NIH; 1999.Google Scholar
  3. 3.
    Blakely ML, Shamberger RC, Norkool P, Beckwith JB, Green DM, Ritchey ML. Outcome of children with cystic partially differentiated nephroblastoma treated with or without chemotherapy. J Pediatr Surg. 2003;38:897–900.PubMedCrossRefGoogle Scholar
  4. 4.
    Beckwith JB, Zuppan CE, Browning NG, Moksness J, Breslow NE. Histological analysis of aggressiveness and responsiveness in Wilms’ tumor. Med Pediatr Oncol. 1996;27:422–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Dome JS, Cotton CA, Perlman EJ, et al. Treatment of anaplastic histology Wilms’ tumor: results from the fifth National Wilms’ Tumor Study. J Clin Oncol. 2006;24:2352–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Vujanic GM, Harms D, Sandstedt B, Weirich A, de Kraker J, Delemarre JF. New definitions of focal and diffuse anaplasia in Wilms tumor: the International Society of Paediatric Oncology (SIOP) experience. Med Pediatr Oncol. 1999;32:317–23.PubMedCrossRefGoogle Scholar
  7. 7.
    Faria P, Beckwith JB, Mishra K, et al. Focal versus diffuse anaplasia in Wilms tumor—new definitions with prognostic significance: a report from the National Wilms Tumor Study Group. Am J Surg Pathol. 1996;20:909–20.PubMedCrossRefGoogle Scholar
  8. 8.
    Beckwith JB, Kiviat NB, Bonadio JF. Nephrogenic rests, nephroblastomatosis, and the pathogenesis of Wilms’ tumor. Pediatr Pathol. 1990;10:1–36.PubMedCrossRefGoogle Scholar
  9. 9.
    Pizzo PAPDG. Principles and practice of pediatric oncology. 6th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins; 2011.Google Scholar
  10. 10.
    Choufani S, Shuman C, Weksberg R. Beckwith-Wiedemann syndrome. Am J Med Genet C Semin Med Genet. 2010;154C:343–54.PubMedCrossRefGoogle Scholar
  11. 11.
    Cerrato F, Vernucci M, Pedone PV, et al. The 5′ end of the KCNQ1OT1 gene is hypomethylated in the Beckwith-Wiedemann syndrome. Hum Genet. 2002;111:105–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Bliek J, Maas SM, Ruijter JM, et al. Increased tumour risk for BWS patients correlates with aberrant H19 and not KCNQ1OT1 methylation: occurrence of KCNQ1OT1 hypomethylation in familial cases of BWS. Hum Mol Genet. 2001;10:467–76.PubMedCrossRefGoogle Scholar
  13. 13.
    Weksberg R, Nishikawa J, Caluseriu O, et al. Tumor development in the Beckwith-Wiedemann syndrome is associated with a variety of constitutional molecular 11p15 alterations including imprinting defects of KCNQ1OT1. Hum Mol Genet. 2001;10:2989–3000.PubMedCrossRefGoogle Scholar
  14. 14.
    Shuman C, Smith AC, Steele L, et al. Constitutional UPD for chromosome 11p15 in individuals with isolated hemihyperplasia is associated with high tumor risk and occurs following assisted reproductive technologies. Am J Med Genet A. 2006;140:1497–503.PubMedGoogle Scholar
  15. 15.
    Royer-Pokora B, Graf N. Wilms tumors arising at young age: a genetic basis to distinguish subgroups for individualized therapy. J Clin Oncol. 2011;29:e485–6. Author reply e7–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Gronskov K, Olsen JH, Sand A, et al. Population-based risk estimates of Wilms tumor in sporadic aniridia. A comprehensive mutation screening procedure of PAX6 identifies 80% of mutations in aniridia. Hum Genet. 2001;109:11–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Scott RH, Walker L, Olsen OE, et al. Surveillance for Wilms tumour in at-risk children: pragmatic recommendations for best practice. Arch Dis Child. 2006;91:995–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Green DM, Breslow NE, Beckwith JB, Norkool P. Screening of children with hemihypertrophy, aniridia, and Beckwith-Wiedemann syndrome in patients with Wilms tumor: a report from the National Wilms Tumor Study. Med Pediatr Oncol. 1993;21:188–92.PubMedCrossRefGoogle Scholar
  19. 19.
    Paulino AC, Thakkar B, Henderson WG. Metachronous bilateral Wilms’ tumor: the importance of time interval to the development of a second tumor. Cancer. 1998;82:415–20.PubMedCrossRefGoogle Scholar
  20. 20.
    Coppes MJ, Arnold M, Beckwith JB, et al. Factors affecting the risk of contralateral Wilms tumor development: a report from the National Wilms Tumor Study Group. Cancer. 1999; 85:1616–25.PubMedCrossRefGoogle Scholar
  21. 21.
    Rivera MN, Kim WJ, Wells J, et al. An X chromosome gene, WTX, is commonly inactivated in Wilms tumor. Science. 2007;315:642–5.PubMedCrossRefGoogle Scholar
  22. 22.
    Rivera MN, Kim WJ, Wells J, et al. The tumor suppressor WTX shuttles to the nucleus and modulates WT1 activity. Proc Natl Acad Sci U S A. 2009;106:8338–43.PubMedCrossRefGoogle Scholar
  23. 23.
    Su MC, Huang WC, Lien HC. Beta-catenin expression and mutation in adult and pediatric Wilms’ tumors. APMIS. 2008;116:771–8.PubMedCrossRefGoogle Scholar
  24. 24.
    Major MB, Camp ND, Berndt JD, et al. Wilms tumor suppressor WTX negatively regulates WNT/beta-catenin signaling. Science. 2007;316:1043–6.PubMedCrossRefGoogle Scholar
  25. 25.
    Cancer NR. Converging on beta-catenin in Wilms tumor. Science. 2007;316:988–9.CrossRefGoogle Scholar
  26. 26.
    Koesters R, Ridder R, Kopp-Schneider A, et al. Mutational activation of the beta-catenin proto-oncogene is a common event in the development of Wilms’ tumors. Cancer Res. 1999;59:3880–2.PubMedGoogle Scholar
  27. 27.
    Ruteshouser EC, Robinson SM, Huff V. Wilms tumor genetics: mutations in WT1, WTX, and CTNNB1 account for only about one-third of tumors. Genes Chromosomes Cancer. 2008; 47:461–70.PubMedCrossRefGoogle Scholar
  28. 28.
    Grundy PE, Breslow NE, Li S, et al. Loss of heterozygosity for chromosomes 1p and 16q is an adverse prognostic factor in favorable-histology Wilms tumor: a report from the National Wilms Tumor Study Group. J Clin Oncol. 2005;23:7312–21.PubMedCrossRefGoogle Scholar
  29. 29.
    Breslow N, Churchill G, Beckwith JB, et al. Prognosis for Wilms’ tumor patients with nonmetastatic disease at diagnosis—results of the second National Wilms’ Tumor Study. J Clin Oncol. 1985;3:521–31.PubMedGoogle Scholar
  30. 30.
    Burger D, Moorman-Voestermans CG, Mildenberger H, et al. The advantages of preoperative therapy in Wilms’ tumour. A summarised report on clinical trials conducted by the International Society of Paediatric Oncology (SIOP). Z Kinderchir. 1985;40:170–5.PubMedGoogle Scholar
  31. 31.
    Gommersall LM, Arya M, Mushtaq I, Duffy P. Current challenges in Wilms’ tumor management. Nat Clin Pract Oncol. 2005;2:298–304. Quiz 1 p following 24.PubMedCrossRefGoogle Scholar
  32. 32.
    van den Heuvel-Eibrink MM, Grundy P, Graf N, et al. Characteristics and survival of 750 children diagnosed with a renal tumor in the first seven months of life: a collaborative study by the SIOP/GPOH/SFOP, NWTSG, and UKCCSG Wilms tumor study groups. Pediatr Blood Cancer. 2008;50:1130–4.PubMedCrossRefGoogle Scholar
  33. 33.
    Vujanic GM, Kelsey A, Mitchell C, Shannon RS, Gornall P. The role of biopsy in the diagnosis of renal tumors of childhood: results of the UKCCSG Wilms tumor study 3. Med Pediatr Oncol. 2003;40:18–22.PubMedCrossRefGoogle Scholar
  34. 34.
    Shet T, Viswanathan S. The cytological diagnosis of paediatric renal tumours. J Clin Pathol. 2009;62:961–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Shamberger RC, Anderson JR, Breslow NE, et al. Long-term outcomes for infants with very low risk Wilms tumor treated with surgery alone in National Wilms Tumor Study-5. Ann Surg. 2010;251:555–8.PubMedCrossRefGoogle Scholar
  36. 36.
    Sredni ST, Gadd S, Huang CC, et al. Subsets of very low risk Wilms tumor show distinctive gene expression, histologic, and clinical features. Clin Cancer Res. 2009;15:6800–9.PubMedCrossRefGoogle Scholar
  37. 37.
    Perlman EJ, Grundy PE, Anderson JR, et al. WT1 mutation and 11P15 loss of heterozygosity predict relapse in very low-risk Wilms tumors treated with surgery alone: a children’s oncology group study. J Clin Oncol. 2011;29:698–703.PubMedCrossRefGoogle Scholar
  38. 38.
    Bruder E, Passera O, Harms D, et al. Morphologic and molecular characterization of renal cell carcinoma in children and young adults. Am J Surg Pathol. 2004;28:1117–32.PubMedCrossRefGoogle Scholar
  39. 39.
    Selle B, Furtwangler R, Graf N, Kaatsch P, Bruder E, Leuschner I. Population-based study of renal cell carcinoma in children in Germany, 1980–2005: more frequently localized tumors and underlying disorders compared with adult counterparts. Cancer. 2006;107:2906–14.PubMedCrossRefGoogle Scholar
  40. 40.
    Eble JN. Pathology and genetics of tumours of the urinary system and male genital organs. Lyon: IARC Press, Oxford; 2004.Google Scholar
  41. 41.
    Perlman EJ. Pediatric renal cell carcinoma. Surg Pathol Clin. 2010;3:641–51.PubMedCrossRefGoogle Scholar
  42. 42.
    Argani P, Antonescu CR, Couturier J, et al. PRCC-TFE3 renal carcinomas: morphologic, immunohistochemical, ultrastructural, and molecular analysis of an entity associated with the t(X;1)(p11.2;q21). Am J Surg Pathol. 2002;26:1553–66.PubMedCrossRefGoogle Scholar
  43. 43.
    Argani P, Antonescu CR, Illei PB, et al. Primary renal neoplasms with the ASPL-TFE3 gene fusion of alveolar soft part sarcoma: a distinctive tumor entity previously included among renal cell carcinomas of children and adolescents. Am J Pathol. 2001;159:179–92.PubMedCrossRefGoogle Scholar
  44. 44.
    Argani P, Hawkins A, Griffin CA, et al. A distinctive pediatric renal neoplasm characterized by epithelioid morphology, basement membrane production, focal HMB45 immunoreactivity, and t(6;11)(p21.1;q12) chromosome translocation. Am J Pathol. 2001;158:2089–96.PubMedCrossRefGoogle Scholar
  45. 45.
    Argani P, Lae M, Hutchinson B, et al. Renal carcinomas with the t(6;11)(p21;q12): clinicopathologic features and demonstration of the specific alpha-TFEB gene fusion by immunohistochemistry, RT-PCR, and DNA PCR. Am J Surg Pathol. 2005;29:230–40.PubMedCrossRefGoogle Scholar
  46. 46.
    Malouf GG, Camparo P, Molinie V, et al. Transcription factor E3 and transcription factor EB renal cell carcinomas: clinical features, biological behavior and prognostic factors. J Urol. 2011;185:24–9.PubMedCrossRefGoogle Scholar
  47. 47.
    Argani P, Lal P, Hutchinson B, Lui MY, Reuter VE, Ladanyi M. Aberrant nuclear immunoreactivity for TFE3 in neoplasms with TFE3 gene fusions: a sensitive and specific immunohistochemical assay. Am J Surg Pathol. 2003;27:750–61.PubMedCrossRefGoogle Scholar
  48. 48.
    Argani P, Aulmann S, Karanjawala Z, Fraser RB, Ladanyi M, Rodriguez MM. Melanotic Xp11 translocation renal cancers: a distinctive neoplasm with overlapping features of PEComa, carcinoma, and melanoma. Am J Surg Pathol. 2009;33:609–19.PubMedCrossRefGoogle Scholar
  49. 49.
    Argani P, Perlman EJ, Breslow NE, et al. Clear cell sarcoma of the kidney: a review of 351 cases from the National Wilms Tumor Study Group Pathology Center. Am J Surg Pathol. 2000;24:4–18.PubMedCrossRefGoogle Scholar
  50. 50.
    Seibel NL, Li S, Breslow NE, et al. Effect of duration of treatment on treatment outcome for patients with clear-cell sarcoma of the kidney: a report from the National Wilms’ Tumor Study Group. J Clin Oncol. 2004;22:468–73.PubMedCrossRefGoogle Scholar
  51. 51.
    Radulescu VC, Gerrard M, Moertel C, et al. Treatment of recurrent clear cell sarcoma of the kidney with brain metastasis. Pediatr Blood Cancer. 2008;50:246–9.PubMedCrossRefGoogle Scholar
  52. 52.
    Marsden HB, Lawler W, Kumar PM. Bone metastasizing renal tumor of childhood: morphological and clinical features, and differences from Wilms’ tumor. Cancer. 1978;42:1922–8.PubMedCrossRefGoogle Scholar
  53. 53.
    Beckwith JB, Larson E. Case 7. Clear cell sarcoma of kidney. Pediatr Pathol. 1989;9:211–8.PubMedCrossRefGoogle Scholar
  54. 54.
    Schuster AE, Schneider DT, Fritsch MK, Grundy P, Perlman EJ. Genetic and genetic expression analyses of clear cell sarcoma of the kidney. Lab Invest. 2003;83:1293–9.PubMedCrossRefGoogle Scholar
  55. 55.
    Palmer NF, Sutow W. Clinical aspects of the rhabdoid tumor of the kidney: a report of the National Wilms’ Tumor Study Group. Med Pediatr Oncol. 1983;11:242–5.PubMedCrossRefGoogle Scholar
  56. 56.
    Amar AM, Tomlinson G, Green DM, Breslow NE, de Alarcon PA. Clinical presentation of rhabdoid tumors of the kidney. J Pediatr Hematol Oncol. 2001;23:105–8.PubMedCrossRefGoogle Scholar
  57. 57.
    Vujanic GM, Sandstedt B, Harms D, Boccon-Gibod L, Delemarre JF. Rhabdoid tumour of the kidney: a clinicopathological study of 22 patients from the International Society of Paediatric Oncology (SIOP) nephroblastoma file. Histopathology. 1996;28:333–40.PubMedCrossRefGoogle Scholar
  58. 58.
    Versteege I, Sevenet N, Lange J, et al. Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer. Nature. 1998;394:203–6.PubMedCrossRefGoogle Scholar
  59. 59.
    Biegel JA, Zhou JY, Rorke LB, Stenstrom C, Wainwright LM, Fogelgren B. Germ-line and acquired mutations of INI1 in atypical teratoid and rhabdoid tumors. Cancer Res. 1999; 59:74–9.PubMedGoogle Scholar
  60. 60.
    Biegel JA. Molecular genetics of atypical teratoid/rhabdoid tumor. Neurosurg Focus. 2006;20:E11.PubMedCrossRefGoogle Scholar
  61. 61.
    Pettinato G, Manivel JC, Wick MR, Dehner LP. Classical and cellular (atypical) congenital mesoblastic nephroma: a clinicopathologic, ultrastructural, immunohistochemical, and flow cytometric study. Hum Pathol. 1989;20:682–90.PubMedCrossRefGoogle Scholar
  62. 62.
    Knezevich SR, Garnett MJ, Pysher TJ, Beckwith JB, Grundy PE, Sorensen PH. ETV6-NTRK3 gene fusions and trisomy 11 establish a histogenetic link between mesoblastic nephroma and congenital fibrosarcoma. Cancer Res. 1998;58:5046–8.PubMedGoogle Scholar
  63. 63.
    Dubus P, Coindre JM, Groppi A, et al. The detection of Tel-TrkC chimeric transcripts is more specific than TrkC immunoreactivity for the diagnosis of congenital fibrosarcoma. J Pathol. 2001;193:88–94.PubMedCrossRefGoogle Scholar
  64. 64.
    Knezevich SR, McFadden DE, Tao W, Lim JF, Sorensen PH. A novel ETV6-NTRK3 gene fusion in congenital fibrosarcoma. Nat Genet. 1998;18:184–7.PubMedCrossRefGoogle Scholar
  65. 65.
    Furtwaengler R, Reinhard H, Leuschner I, et al. Mesoblastic nephroma—a report from the Gesellschaft fur Padiatrische Onkologie und Hamatologie (GPOH). Cancer. 2006;106: 2275–83.PubMedCrossRefGoogle Scholar
  66. 66.
    Yang K, Lui WO, Xie Y, et al. Co-existence of SYT-SSX1 and SYT-SSX2 fusions in synovial sarcomas. Oncogene. 2002;21:4181–90.PubMedCrossRefGoogle Scholar
  67. 67.
    Crew AJ, Clark J, Fisher C, et al. Fusion of SYT to two genes, SSX1 and SSX2, encoding proteins with homology to the Kruppel-associated box in human synovial sarcoma. EMBO J. 1995;14:2333–40.PubMedGoogle Scholar
  68. 68.
    Panagopoulos I, Mertens F, Isaksson M, et al. Clinical impact of molecular and cytogenetic findings in synovial sarcoma. Genes Chromosomes Cancer. 2001;31:362–72.PubMedCrossRefGoogle Scholar
  69. 69.
    Agus V, Tamborini E, Mezzelani A, Pierotti MA, Pilotti S. Re: a novel fusion gene, SYT-SSX4, in synovial sarcoma. J Natl Cancer Inst. 2001;93:1347–9.PubMedCrossRefGoogle Scholar
  70. 70.
    Bijwaard KE, Fetsch JF, Przygodzki R, Taubenberger JK, Lichy JH. Detection of SYT-SSX fusion transcripts in archival synovial sarcomas by real-time reverse transcriptase-polymerase chain reaction. J Mol Diagn. 2002;4:59–64.PubMedCrossRefGoogle Scholar
  71. 71.
    Storlazzi CT, Mertens F, Mandahl N, et al. A novel fusion gene, SS18L1/SSX1, in synovial sarcoma. Genes Chromosomes Cancer. 2003;37:195–200.PubMedCrossRefGoogle Scholar
  72. 72.
    Bernstein M, Kovar H, Paulussen M, et al. Ewing’s sarcoma family of tumors: current management. Oncologist. 2006;11:503–19.PubMedCrossRefGoogle Scholar
  73. 73.
    Gerald WL, Rosai J, Ladanyi M. Characterization of the genomic breakpoint and chimeric transcripts in the EWS-WT1 gene fusion of desmoplastic small round cell tumor. Proc Natl Acad Sci U S A. 1995;92:1028–32.PubMedCrossRefGoogle Scholar
  74. 74.
    Antonescu CR, Gerald WL, Magid MS, Ladanyi M. Molecular variants of the EWS-WT1 gene fusion in desmoplastic small round cell tumor. Diagn Mol Pathol. 1998;7:24–8.PubMedCrossRefGoogle Scholar
  75. 75.
    Murphy AJ, Bishop K, Pereira C, et al. A new molecular variant of desmoplastic small round cell tumor: significance of WT1 immunostaining in this entity. Hum Pathol. 2008;39:1763–70.PubMedCrossRefGoogle Scholar
  76. 76.
    Coleman JA, Russo P. Hereditary and familial kidney cancer. Curr Opin Urol. 2009;19:478–85.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  1. 1.Department of Pathology, Molecular Diagnostic Laboratory, Ann and Robert H. Lurie Children’s Hospital of ChicagoNorthwestern University’s Feinberg School of MedicineChicagoUSA

Personalised recommendations