Skip to main content
SpringerLink
Log in

Usefulness of a break-apart FISH assay in the diagnosis of Xp11.2 translocation renal cell carcinoma

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

Xp11.2 translocation renal cell carcinoma (RCC) is a rare subtype of RCC predominantly reported in young patients. It results from gene fusions between the transcription factor E3 (TFE3) gene, which is located on chromosome Xp11.2, and various fusion partners. Recently, a dual color, break-apart fluorescence in situ hybridization (FISH) assay to detect Xp11.2 translocation was reported. We performed this study to evaluate the usefulness of the FISH assay in the diagnosis of Xp11.2 translocation RCC using a commercially available TFE3 break-apart probe. We immunohistochemically analyzed TFE3 nuclear expression in 809 cases of RCCs using 14 tissue microarray blocks and selected nine cases those showed moderate to strong positive nuclear immunoreactivity for TFE3. The extent of TFE3 nuclear expression was variable. The TFE3 FISH assay was performed in these 9 selected cases and 44 negative control cases. Only four out of nine selected cases showed the TFE3 break-apart signal. TFE3 FISH-positive cases mainly showed diffuse and strong TFE3 immunopositivity, but one case revealed focal and moderate TFE3 staining. On the contrary, TFE3 FISH-negative cases mainly revealed focal and moderate TFE3 immunoreactivity, however, one FISH-negative case revealed diffuse and strong TFE3 nuclear immunopositivity. All negative control cases revealed normal TFE3 FISH results. Our results reveal that TFE3 immunohistochemistry can show false-positive results, and that the TFE3 break-apart FISH assay is a useful complementary method for confirming the diagnosis of Xp11.2 translocation RCC.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Argani P, Antonescu CR, Illei PB, Lui MY, Timmons CF, Newbury R, Reuter VE, Garvin AJ, Perez-Atayde AR, Fletcher JA, Beckwith JB, Bridge JA, Ladanyi M (2001) 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 159(1):179–192

    Article  PubMed  CAS  Google Scholar 

  2. Argani P, Ladanyi M (2005) Translocation carcinomas of the kidney. Clin Lab Med 25(2):363–378

    Article  PubMed  Google Scholar 

  3. Eble JN, Sauter G, Ebstein JI, Sesterhenn IA (eds) (2004) WHO classification of tumors. Pathology and genetics of tumors of the genitourinary and male genital organs. IARC Press, Lyon

    Google Scholar 

  4. Armah HB, Parwani AV (2010) Xp11.2 translocation renal cell carcinoma. Arch Pathol Lab Med 134(1):124–129

    PubMed  Google Scholar 

  5. Argani P, Ladanyi M (2003) Distinctive neoplasms characterised by specific chromosomal translocations comprise a significant proportion of paediatric renal cell carcinomas. Pathology 35(6):492–498

    Article  PubMed  CAS  Google Scholar 

  6. Heimann P, El Housni H, Ogur G, Weterman MA, Petty EM, Vassart G (2001) Fusion of a novel gene, RCC17, to the TFE3 gene in t(X;17)(p11.2;q25.3)-bearing papillary renal cell carcinomas. Cancer Res 61(10):4130–4135

    PubMed  CAS  Google Scholar 

  7. Shipley JM, Birdsall S, Clark J, Crew J, Gill S, Linehan M, Gnarra J, Fisher S, Craig IW, Cooper CS (1995) Mapping the X chromosome breakpoint in two papillary renal cell carcinoma cell lines with a t(X;1)(p11.2;q21.2) and the first report of a female case. Cytogenet Cell Genet 71(3):280–284

    Article  PubMed  CAS  Google Scholar 

  8. Ross H, Argani P (2010) Xp11 translocation renal cell carcinoma. Pathology 42(4):369–373

    Article  PubMed  CAS  Google Scholar 

  9. Komai Y, Fujiwara M, Fujii Y, Mukai H, Yonese J, Kawakami S, Yamamoto S, Migita T, Ishikawa Y, Kurata M, Nakamura T, Fukui I (2009) Adult Xp11 translocation renal cell carcinoma diagnosed by cytogenetics and immunohistochemistry. Clin Cancer Res 15(4):1170–117

    Article  Google Scholar 

  10. Camparo P, Vasiliu V, Molinie V, Couturier J, Dykema KJ, Petillo D, Furge KA, Comperat EM, Lae M, Bouvier R, Boccon-Gibod L, Denoux Y, Ferlicot S, Forest E, Fromont G, Hintzy MC, Laghouati M, Sibony M, Tucker ML, Weber N, Teh BT, Vieillefond A (2008) Renal translocation carcinomas: clinicopathologic, immunohistochemical, and gene expression profiling analysis of 31 cases with a review of the literature. Am J Surg Pathol 32(5):656–670

    Article  PubMed  Google Scholar 

  11. Wu A, Kunju LP, Cheng L, Shah RB (2008) Renal cell carcinoma in children and young adults: analysis of clinicopathological, immunohistochemical and molecular characteristics with an emphasis on the spectrum of Xp11.2 translocation-associated and unusual clear cell subtypes. Histopathology 53(5):533–544

    Article  PubMed  CAS  Google Scholar 

  12. Ramphal R, Pappo A, Zielenska M, Grant R, Ngan BY (2006) Pediatric renal cell carcinoma: clinical, pathologic, and molecular abnormalities associated with the members of the mit transcription factor family. Am J Clin Pathol 126(3):349–364

    Article  PubMed  CAS  Google Scholar 

  13. Zhong M, De Angelo P, Osborne L, Keane-Tarchichi M, Goldfischer M, Edelmann L, Yang Y, Linehan WM, Merino MJ, Aisner S, Hameed M (2010) Dual-color, break-apart FISH assay on paraffin-embedded tissues as an adjunct to diagnosis of Xp11 translocation renal cell carcinoma and alveolar soft part sarcoma. Am J Surg Pathol 34(6):757–766

    Article  PubMed  Google Scholar 

  14. Argani P, Antonescu CR, Couturier J, Fournet JC, Sciot R, Debiec-Rychter M, Hutchinson B, Reuter VE, Boccon-Gibod L, Timmons C, Hafez N, Ladanyi M (2002) 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 26(12):1553–1566

    Article  PubMed  Google Scholar 

  15. Argani P, Olgac S, Tickoo SK, Goldfischer M, Moch H, Chan DY, Eble JN, Bonsib SM, Jimeno M, Lloreta J, Billis A, Hicks J, De Marzo AM, Reuter VE, Ladanyi M (2007) Xp11 translocation renal cell carcinoma in adults: expanded clinical, pathologic, and genetic spectrum. Am J Surg Pathol 31(8):1149–1160

    Article  PubMed  Google Scholar 

  16. Suzigan S, Drut R, Faria P, Argani P, De Marzo AM, Barbosa RN, Mello Denadai ER, Martins-Filho J, Martucci RC, Bauab T Jr (2007) Xp11 translocation carcinoma of the kidney presenting with multilocular cystic renal cell carcinoma-like features. Int J Surg Pathol 15(2):199–203

    Article  PubMed  Google Scholar 

  17. Argani P, Lal P, Hutchinson B, Lui MY, Reuter VE, Ladanyi M (2003) Aberrant nuclear immunoreactivity for TFE3 in neoplasms with TFE3 gene fusions: a sensitive and specific immunohistochemical assay. Am J Surg Pathol 27(6):750–761

    Article  PubMed  Google Scholar 

  18. Martignoni G, Pea M, Gobbo S, Brunelli M, Bonetti F, Segala D, Pan CC, Netto G, Doglioni C, Hes O, Argani P, Chilosi M (2009) Cathepsin-K immunoreactivity distinguishes MiTF/TFE family renal translocation carcinomas from other renal carcinomas. Mod Pathol 22(8):1016–1022

    Article  PubMed  CAS  Google Scholar 

  19. Armah HB, Parwani AV (2008) Renal cell carcinoma in a 33-year-old male with an unusual morphology and an aggressive clinical course: possible Xp11.2 translocation. Pathology 40(3):306–308

    Article  PubMed  CAS  Google Scholar 

  20. Armah HB, Parwani AV, Surti U, Bastacky SI (2009) Xp11.2 translocation renal cell carcinoma occurring during pregnancy with a novel translocation involving chromosome 19: a case report with review of the literature. Diagn Pathol 4:15

    Article  PubMed  Google Scholar 

  21. Kuroda N, Tamura M, Tanaka Y, Hes O, Michal M, Inoue K, Ohara M, Mizuno K, Lee GH (2009) Adult-onset renal cell carcinoma associated with Xp11.2 translocations/TFE3 gene fusion with smooth muscle stroma and abnormal vessels. Pathol Int 59(7):486–491

    Article  PubMed  Google Scholar 

  22. LaGrange CA, Lele SM, Strup SE (2007) Renal cell carcinoma associated with TFE3 gene fusion in an elderly woman. Urology 70(3):590 e511–592

    Article  Google Scholar 

  23. Meyer PN, Clark JI, Flanigan RC, Picken MM (2007) Xp11.2 translocation renal cell carcinoma with very aggressive course in five adults. Am J Clin Pathol 128(1):70–79

    Article  PubMed  CAS  Google Scholar 

  24. Tanas MR, Goldblum JR (2009) Fluorescence in situ hybridization in the diagnosis of soft tissue neoplasms: a review. Adv Anat Pathol 16(6):383–391

    Article  PubMed  CAS  Google Scholar 

  25. Geller JI, Argani P, Adeniran A, Hampton E, De Marzo A, Hicks J, Collins MH (2008) Translocation renal cell carcinoma: lack of negative impact due to lymph node spread. Cancer 112(7):1607–1616

    Article  PubMed  Google Scholar 

  26. Argani P, Aulmann S, Illei PB, Netto GJ, Ro J, Cho HY, Dogan S, Ladanyi M, Martignoni G, Goldblum JR, Weiss SW (2010) A distinctive subset of PEComas harbors TFE3 gene fusions. Am J Surg Pathol 34(10):1395–1406

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (A080239).

Conflict of interest statement

We declare that we have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Pathology and Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine, 28 Chongno-gu Yongon-dong, Seoul, 110-799, South Korea

    Soo Hee Kim, Yoomi Choi, Hae Yeon Jeong, Kyoungbun Lee, Ji Youn Chae & Kyung Chul Moon

  2. Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, South Korea

    Kyung Chul Moon

Authors
  1. Soo Hee Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yoomi Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hae Yeon Jeong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kyoungbun Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ji Youn Chae
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kyung Chul Moon
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kyung Chul Moon.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, S.H., Choi, Y., Jeong, H.Y. et al. Usefulness of a break-apart FISH assay in the diagnosis of Xp11.2 translocation renal cell carcinoma. Virchows Arch 459, 299–306 (2011). https://doi.org/10.1007/s00428-011-1127-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-011-1127-5

Keywords

Search

Navigation