Skip to main content

Advertisement

SpringerLink
Log in

Detection of ASPL/TFE3 fusion transcripts and the TFE3 antigen in formalin-fixed, paraffin-embedded tissue in a series of 18 cases of alveolar soft part sarcoma: Useful diagnostic tools in cases with unusual histological features

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

Abstract

Alveolar soft part sarcoma (ASPS) is a rare malignancy; diagnostic problems may occur when cases present as a metastasis or with unusual morphologic features. In this study, a series of 18 cases with follow-up information were analysed with regard to the ASPL/TFE3 fusion transcripts and immuno-detection of TFE3 using archival formalin-fixed, paraffin-embedded tissues. Novel primers to detect ASPL/TFE3 fusion transcripts, type 1 and 2, were designed. The patients, ten female and eight male, ranged in age from 3 to 46 years; 16 involved soft tissues of the extremities (nine, lower; seven, upper), one involved the uterine cervix and one was a primary bone tumour of the foot. Seven ASPS had unusual morphologic features lacking the typical alveolar pattern. Seven had lung metastases at the time of diagnosis, and three developed lung and brain metastases later. Four patients died of disease (after 1–5 years); four are alive with metastases (after 2–15 years), and ten are alive and well (after 1–10 years). Vascular invasion correlated with metastatic disease. All 18 ASPS, four granular cell tumours (one of which was malignant) and one adrenal cortical carcinoma showed TFE3 immuno-positivity. The 18/18 ASPS showed ASPL/TFE3 fusion transcripts (nine, type 1; nine, type 2), four of which had a balanced translocation. ASPL/TFE3 fusion transcripts were not detected in 25 controls. We conclude that immuno-detection of TFE3 and RT-PCR-based identification of ASPL/TFE3 fusion transcripts in formalin-fixed, paraffin-embedded tissues are powerful tools in the diagnosis of ASPS, particularly in cases with unusual morphologic features.

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
Fig. 3

Similar content being viewed by others

References

  1. Christopherson WM, Foote FW Jr, Stewart FW (1952) Alveolar soft part sarcomas: structurally characteristic tumors of uncertain histogenesis. Cancer 5:100–111

    Article  PubMed  CAS  Google Scholar 

  2. Folpe AL, Deyrup AT (2006) Alveolar soft-part sarcoma: a review and update. J Clin Pathol 59:1127–1132

    Article  PubMed  CAS  Google Scholar 

  3. Fadare O (2006) Uncommon sarcomas of the uterine cervix: a review of selected entities. Diagn Pathol 1:30

    Article  PubMed  Google Scholar 

  4. Flieder DB, Moran CA, Suster S (1997) Primary alveolar soft-part sarcoma of the mediastinum: a clinicopathological and immunohistochemical study of two cases. Histopathology 31:469–473

    Article  PubMed  CAS  Google Scholar 

  5. Yagihashi S, Yagihashi N, Hase Y, Nagai K, Alguacil-Garcia A (1991) Primary alveolar soft-part sarcoma of stomach. Am J Surg Pathol 15(4):399–406

    Article  PubMed  CAS  Google Scholar 

  6. Wu J, Brinker DA, Haas M, Montgomery EA, Argani P (2005) Primary alveolar soft part sarcoma (ASPS) of the breast. Int J Surg Pathol 13(1):81–85

    Article  PubMed  Google Scholar 

  7. Liu T-T, Chou Y-H, Lai C-R, Chen C-M, Tsou M-H, Lin H-H, Tiu C-M (1997) Breast mass due to alveolar soft part sarcoma of the pectoris major muscle. Eur J Radiol 24:57–59

    Article  PubMed  CAS  Google Scholar 

  8. Aisner SC, Beebe K, Blacksin M, Mirani N, Hameed M (2008) Primary alveolar soft part sarcoma of fibula demonstrating ASPL-TFE3 fusion: a case report and review of the literature. Skeletal Radiol 37:1047–1051

    Article  PubMed  Google Scholar 

  9. Park Y-K, Unni KK, Kim YW et al (1999) Primary alveolar soft part sarcoma of bone. Histopathology 35:411–417

    Article  PubMed  CAS  Google Scholar 

  10. Amin MB, Patel RM, Oliveira P et al (2006) Alveolar soft-part sarcoma of the urinary bladder with urethral recurrence: a unique case with emphasis on differential diagnoses and diagnostic utility of an immunohistochemical panel including TFE3. Am J Surg Pathol 30:1322–1325

    Article  PubMed  Google Scholar 

  11. Weiss SW, Goldblum JR. Enzinger and Weiss’s soft tissue tumors fifth edition (2008). Mosby Elsevier 1182-1191

  12. Zarrin-Khameh N, Kaye KS (2007) Alveolar soft part sarcoma. Arch Pathol Lab Med 131:488–491

    PubMed  Google Scholar 

  13. Ladanyi M, Lui MY, Antonescu CR et al (2001) The der(17)t(X;17)(p11;q25) of human alveolar soft part sarcoma fuses the TFE3 transcription factor gene to ASPL, a novel gene at 17q25. Oncogene 20:48–57

    Article  PubMed  CAS  Google Scholar 

  14. Aulmann S, Longerich T, Schirmacher P, Mechtersheimer G, Penzel R (2007) Detection of the ASPSCR1-TFE3 gene fusion in paraffin-embedded alveolar soft part sarcomas. Histopathology 50:881–886

    Article  PubMed  CAS  Google Scholar 

  15. Argani P, Antonescu CR, Illei PB et al (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 159:179–192

    Article  PubMed  CAS  Google Scholar 

  16. 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 

  17. Mangham DC, Williams A, McMullan DJ, McClure J, Sumathi VP, Grimer RJ, Davies AM (2006) Ewing’s sarcoma of bone: the detection of specific transcripts in a large, consecutive series of formalin-fixed, decalcified, paraffin-embedded tissue samples using the reverse transcriptase-polymerase chain reaction. Histopathology 48:363–376

    Article  PubMed  CAS  Google Scholar 

  18. Sorg I, Metzler A (1995) Detection of Borna disease virus RNA in formalin-fixed, paraffin-embedded brain tissues by nested PCR. J Clin Microbiol 33(4):821–823

    PubMed  CAS  Google Scholar 

  19. Fletcher CDM, Unni KK, Mertens F (eds) (2002) World Health Organization classification of tumours. Pathology and genetics of tumours of soft tissue and bone, IARC Press

    Google Scholar 

  20. Koguchi Y, Yamaguchi T, Yamato M, Osada D, Saotome K (2005) Alveolar soft part sarcoma of bone. J Orthop Sci 10:652–655

    Article  PubMed  Google Scholar 

  21. Durkin RC, Johnston JO (1999) Alveolar soft part sarcoma involving the ilium. Clin Orthop Relat Res 359:197–202

    Article  PubMed  Google Scholar 

  22. Zhu FP, Lu GM, Zhang LJ, Wang JD, An XJ, Dong YC (2009) Primary alveolar soft part sarcoma of vertebra: a case report and literature review. Skeletal Radiol 38(8):825–829

    Article  PubMed  Google Scholar 

  23. Heimann P, Devalck C, Dubusscher C, Sariban E, Vamos E (1998) Alveolar soft-part sarcoma: further evidence by FISH for the involvement of chromosome band 17q25. Genes Chromosom Cancer 23:194–197

    Article  PubMed  CAS  Google Scholar 

  24. Hernandez-Marti MJ, Orellana-Alonso C, Badia-Garrabou L, Miralles AV, Paradis-Alos A (1995) Renal adenocarcinoma in an 8-year-old child, with a t(X;17)(p11.2;q25). Cancer Genet Cytogenet 83:82–83

    Article  PubMed  CAS  Google Scholar 

  25. Pang LJ, Chang B, Zou H et al (2008) Alveolar soft part sarcoma. A biomarker diagnostic strategy using TFE3 immunoassay and ASPL-TFE3 fusion transcripts in paraffin-embedded tumor tissues. Diagn Mol Pathol 17(4):245–252

    Article  PubMed  CAS  Google Scholar 

  26. Uppal S, Aviv H, Patterson F, Cohen S, Benevenia J, Aisner S, Hameed M (2003) Alveolar soft part sarcoma-reciprocal translocation between chromosome 17q25 and Xp11. Report of a case with metastases at presentation and review of the literature. Acta Orthop Belg 69(2):182–187

    PubMed  CAS  Google Scholar 

  27. Petit MM, Mols R, Schoenmakers EF, Mandahl N, Van de Ven WJ (1996) LPP, the preferred fusion partner gene of HMGIC in lipomas, is a novel member of the LIM protein gene family. Genomics 36:118–129

    Article  PubMed  CAS  Google Scholar 

  28. Rogalla P, Lemke I, Kazmierczak B, Bullerdiek J (2000) An identical HMGIC-LPP fusion transcript is consistently expressed in pulmonary chondroid hamartomas with t(3;12)(q27-28;q14-15). Genes Chromosom Cancer 29:363–366

    Article  PubMed  CAS  Google Scholar 

  29. Dahlén A, Mertens F, Rydholm A et al (2003) Fusion, disruption and expression of HMGA2 in bone and soft tissue chondromas. Mod Pathol 16:1132–1140

    Article  PubMed  Google Scholar 

  30. Knezevich SR, Garnett MJ, Pysher TJ, Beckwith JB, Grundy PE, Sorensen PH (1998) ETV6-NTRK3 gene fusions and trisomy 11 establish a histogenetic link between mesoblastic nephroma and congenital fibrosarcoma. Cancer Res 58:5046–5048

    PubMed  CAS  Google Scholar 

  31. Knezevich SR, McFadden DE, Tao W, Lim JF, Sorensen PH (1998) A novel ETV6-NTRK3 gene fusion in congenital fibrosarcoma. Nat Genet 18:184–187

    Article  PubMed  CAS  Google Scholar 

  32. Rubin BP, Chen CJ, Morgan TW et al (1998) Congenital mesoblastic nephroma t(12;15) is associated with ETV6-NTRK3 gene fusion: cytogenetics and molecular relationship to congenital (infantile) fibrosarcoma. Am J Pathol 153:1451–1458

    Article  PubMed  CAS  Google Scholar 

  33. Eguchi M, Eguchi-Ishimae M, Tojo A et al (1999) Fusion of ETV6 to neutrotrophin-3 receptor TRKC in acute myeloid leukemia with t(12;15)(p13;q25). Blood 93:1355–1363

    PubMed  CAS  Google Scholar 

  34. Tognon C, Knezevich SR, Huntsman D et al (2002) Expression of the ETV6-NTRK3 gene fusion as a primary event in human secretory breast carcinoma. Cancer Cell 2:367–376

    Article  PubMed  CAS  Google Scholar 

  35. Panagopoulos I, Aman P, Fioretos T et al (1994) Fusion of the FUS gene with ERG in acute myeloid leukemia with t(16;21)(p11;q22). Genes Chromosom Cancer 11:256–262

    Article  PubMed  CAS  Google Scholar 

  36. Shing DC, McMullan DJ, Roberts P et al (2003) FUS/ERG gene fusions in Ewing’s tumors. Cancer Res 63:4568–4576

    PubMed  CAS  Google Scholar 

  37. Hallor KH, Mertens F, Jin Y et al (2005) Fusion of the EWSR1 and ATF1 genes without expression of the MITF-M transcript in angiomatoid fibrous histiocytomas. Genes Chromosom Cancer 44:97–102

    Article  PubMed  CAS  Google Scholar 

  38. Hallor KH, Micci F, Meis-Kindblom JM et al (2007) Fusion genes in angiomatoid fibrous histiocytoma. Cancer Lett 251:158–163

    Article  PubMed  CAS  Google Scholar 

  39. Antonescu CR, Nafa K, Segal NH, Cin PD, Ladanyi M (2006) EWS-CREB1: a recurrent variant fusion in clear cell sarcoma – association with gastrointestinal location and absence of melanocytic differentiation. Clin Cancer Res 12(18):5356–5362

    Article  PubMed  CAS  Google Scholar 

  40. Rossi S, Szuhai K, Ijszenga M et al (2007) EWSR1-CREB1 and EWSR1-ATF1 fusion genes in angiomatoid fibrous histiocytoma. Clin Cancer Res 13(24):7322–7328

    Article  PubMed  CAS  Google Scholar 

  41. Fanburg-Smith JC, Meis-Kindblom JM, Fante R et al (1999) Malignant granular cell tumor of soft tissue: diagnostic criteria and clinicopathologic correlation. Am J Surg Pathol 23(1):136

    Article  Google Scholar 

  42. Vistica DT, Krosky PM, Kenny S, Raffeld M, Shoemaker RH (2008) Immunohistochemical discrimination between the ASPL-TFE3 fusion proteins of alveolar soft part sarcoma. J pediatr hematol/oncol 30:46–52

    Article  CAS  Google Scholar 

Download references

Acknowledgment

We thank Hamed Ali for his expert assistance with the figure production.

Conflict of interest statement

We declare that we have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Musculoskeletal Pathology and Orthopaedic Oncology, Royal Orthopaedic Hospital NHS Foundation Trust and Division of Cancer Studies, Medical School, University of Birmingham, Birmingham, B15 2TT, UK

    Ann Williams, Gillian Bartle, Vaiyapuri P. Sumathi, D. Chas Mangham, Rob J. Grimer & Lars-Gunnar Kindblom

  2. Department of Pathology, The University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA

    Jeanne M. Meis

Authors
  1. Ann Williams
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gillian Bartle
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vaiyapuri P. Sumathi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jeanne M. Meis
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D. Chas Mangham
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rob J. Grimer
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lars-Gunnar Kindblom
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lars-Gunnar Kindblom.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Williams, A., Bartle, G., Sumathi, V.P. et al. Detection of ASPL/TFE3 fusion transcripts and the TFE3 antigen in formalin-fixed, paraffin-embedded tissue in a series of 18 cases of alveolar soft part sarcoma: Useful diagnostic tools in cases with unusual histological features. Virchows Arch 458, 291–300 (2011). https://doi.org/10.1007/s00428-010-1039-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-010-1039-9

Keywords

Search

Navigation