Skip to main content

Advertisement

SpringerLink
Log in

PAX3/7–FOXO1 fusion status in older rhabdomyosarcoma patient population by fluorescent in situ hybridization

  • Original Paper
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

In pediatric alveolar rhabdomyosarcoma, the PAX3–FOXO1 and PAX7–FOXO1 gene fusions are prognostic indicators, while little is known concerning this disease in older patients. To determine whether PAX3/7–FOXO1 fusion gene status correlates with outcome in adolescent, young adult, and adult rhabdomyosarcoma patients, the histological, immunohistochemical, and clinical characteristics of 105 patients followed at The University of Texas MD Anderson Cancer Center from 1957 to 2001 were evaluated.

Methods

The samples were assembled into a tissue microarray, and fusion gene status was determined by fluorescence in situ hybridization using PAX3, PAX7, and FOXO1 loci-specific probes. The disease characteristics and specific gene fusion were correlated with patient outcomes using the log-rank test.

Results

Fifty-two percent of the samples exhibited a PAX3–FOXO1 fusion, 15% the PAX7–FOXO1 fusion, and 33% were negative for a rearrangement of these loci. The presence of PAX3/7–FOXO1 translocation was significantly associated with a higher frequency of metastatic disease. Although a statistically significant correlation between the PAX3/7–FOXO1 fusion gene status and overall survival was not identified, there was a trend toward better outcomes for patients with fusion-negative RMS.

Conclusions

Therefore, identification of a FOXO1 fusion appears to be an interesting tool for predicting outcomes in older rhabdomyosarcoma patients and is worth further investigations in this rare subgroup of RMS population.

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
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Asmar L, Gehan EA, Newton WA, Webber BL, Marsden HB, van Unnik AJ, Hamoudi AB, Shimada H, Tsokos M, Harms D et al (1994) Agreement among and within groups of pathologists in the classification of rhabdomyosarcoma and related childhood sarcomas. Report of an international study of four pathology classifications. Cancer 74(9):2579–2588

  • Barr FG, Smith LM, Lynch JC, Strzelecki D, Parham DM, Qualman SJ, Breitfeld PP (2006) Examination of gene fusion status in archival samples of alveolar rhabdomyosarcoma entered on the Intergroup Rhabdomyosarcoma Study-III trial: a report from the Children’s Oncology Group. J Mol Diagn 8(2):202–208. doi:10.2353/jmoldx.2006.050124

    Article  PubMed  CAS  Google Scholar 

  • Bleyer A (2005) The adolescent and young adult gap in cancer care and outcome. Curr Probl Pediatr Adolesc Health Care 35(5):182–217. doi:10.1016/j.cppeds.2005.02.001

    Article  PubMed  Google Scholar 

  • Bridge JA, Liu J, Weibolt V, Baker KS, Perry D, Kruger R, Qualman S, Barr F, Sorensen P, Triche T, Suijkerbuijk R (2000) Novel genomic imbalances in embryonal rhabdomyosarcoma revealed by comparative genomic hybridization and fluorescence in situ hybridization: an intergroup rhabdomyosarcoma study. Genes Chromosom Cancer 27(4):337–344. doi:10.1002/(SICI)1098-2264(200004)27:4<337:AID-GCC1>3.0.CO;2-1

    Article  PubMed  CAS  Google Scholar 

  • Chang B, Pang LJ, Qi Y, Liu CX, Cao Y, Li HA, Hu WH, Jiang JF, Zhang WJ, Li F (2009) PAX–FKHR fusion genes and AChR-gamma in Chinese patients with rhabdomyosarcoma: diagnosis using formalin-fixed archival tissues. Int J Surg Pathol 17(1):6–15

    Article  PubMed  CAS  Google Scholar 

  • Crist W, Gehan EA, Ragab AH, Dickman PS, Donaldson SS, Fryer C, Hammond D, Hays DM, Herrmann J, Heyn R et al (1995) The third intergroup rhabdomyosarcoma study. J Clin Oncol 13(3):610–630

    PubMed  CAS  Google Scholar 

  • Crist WM, Anderson JR, Meza JL, Fryer C, Raney RB, Ruymann FB, Breneman J, Qualman SJ, Wiener E, Wharam M, Lobe T, Webber B, Maurer HM, Donaldson SS (2001) Intergroup rhabdomyosarcoma study-IV: results for patients with nonmetastatic disease. J Clin Oncol 19(12):3091–3102

    PubMed  CAS  Google Scholar 

  • Davis RJ, D’Cruz CM, Lovell MA, Biegel JA, Barr FG (1994) Fusion of PAX7 to FKHR by the variant t(1;13)(p36;q14) translocation in alveolar rhabdomyosarcoma. Cancer Res 54(11):2869–2872

    PubMed  CAS  Google Scholar 

  • Esnaola NF, Rubin BP, Baldini EH, Vasudevan N, Demetri GD, Fletcher CD, Singer S (2001) Response to chemotherapy and predictors of survival in adult rhabdomyosarcoma. Ann Surg 234(2):215–223

    Article  PubMed  CAS  Google Scholar 

  • Ferrari A, Dileo P, Casanova M, Bertulli R, Meazza C, Gandola L, Navarria P, Collini P, Gronchi A, Olmi P, Fossati-Bellani F, Casali PG (2003) Rhabdomyosarcoma in adults. A retrospective analysis of 171 patients treated at a single institution. Cancer 98(3):571–580

    Google Scholar 

  • Hawkins WG, Hoos A, Antonescu CR, Urist MJ, Leung DH, Gold JS, Woodruff JM, Lewis JJ, Brennan MF (2001) Clinicopathologic analysis of patients with adult rhabdomyosarcoma. Cancer 91(4):794–803

    Article  PubMed  CAS  Google Scholar 

  • Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, Thun MJ (2006) Cancer statistics, 2006. CA Cancer J Clin 56(2):106–130

    Article  PubMed  Google Scholar 

  • Kohashi K, Oda Y, Yamamoto H, Tamiya S, Takahira T, Takahashi Y, Tajiri T, Taguchi T, Suita S, Tsuneyoshi M (2008) Alterations of RB1 gene in embryonal and alveolar rhabdomyosarcoma: special reference to utility of pRB immunoreactivity in differential diagnosis of rhabdomyosarcoma subtype. J Cancer Res Clin Oncol 134(10):1097–1103. doi:10.1007/s00432-008-0385-3

    Article  PubMed  CAS  Google Scholar 

  • Little DJ, Ballo MT, Zagars GK, Pisters PW, Patel SR, El-Naggar AK, Garden AS, Benjamin RS (2002) Adult rhabdomyosarcoma: outcome following multimodality treatment. Cancer 95(2):377–388. doi:10.1002/cncr.10669

    Article  PubMed  Google Scholar 

  • Maurer HM, Beltangady M, Gehan EA, Crist W, Hammond D, Hays DM, Heyn R, Lawrence W, Newton W, Ortega J et al (1988) The intergroup rhabdomyosarcoma study-I. A final report. Cancer 61(2):209–220

  • Maurer HM, Gehan EA, Beltangady M, Crist W, Dickman PS, Donaldson SS, Fryer C, Hammond D, Hays DM, Herrmann J et al (1993) The intergroup rhabdomyosarcoma study-II. Cancer 71(5):1904–1922

    Article  PubMed  CAS  Google Scholar 

  • Miettinen M (1988) Rhabdomyosarcoma in patients older than 40 years of age. Cancer 62(9):2060–2065

    Article  PubMed  CAS  Google Scholar 

  • Morotti RA, Nicol KK, Parham DM, Teot LA, Moore J, Hayes J, Meyer W, Qualman SJ (2006) An immunohistochemical algorithm to facilitate diagnosis and subtyping of rhabdomyosarcoma: the Children’s Oncology Group experience. Am J Surg Pathol 30(8):962–968

    Article  PubMed  Google Scholar 

  • Parham DM, Ellison DA (2006) Rhabdomyosarcomas in adults and children: an update. Arch Pathol Lab Med 130(10):1454–1465. doi:10.1043/1543-2165(2006)130[1454:RIAACA]2.0.CO;2

    PubMed  Google Scholar 

  • Raney RB, Anderson JR, Brown KL, Huh WW, Maurer HM, Meyer WH, Parham DM, Rodeberg DA, Wolden SL, Donaldson SS (2010) Treatment results for patients with localized, completely resected (Group I) alveolar rhabdomyosarcoma on intergroup rhabdomyosarcoma study group (IRSG) protocols III and IV, 1984–1997: a report from the Children’s Oncology Group. Pediatr Blood Cancer 55(4):612–616. doi:10.1002/pbc.22520

    Google Scholar 

  • Raney RB, Maurer HM, Anderson JR, Andrassy RJ, Donaldson SS, Qualman SJ, Wharam MD, Wiener ES, Crist WM (2001) The intergroup rhabdomyosarcoma study group (IRSG): major lessons from the IRS-I through IRS-IV studies as background for the current IRS-V treatment protocols. Sarcoma 5(1):9–15. doi:10.1080/13577140120048890

    Article  PubMed  CAS  Google Scholar 

  • Rubin BP, Nishijo K, Chen HI, Yi X, Schuetze DP, Pal R, Prajapati SI, Abraham J, Arenkiel BR, Chen QR, Davis S, McCleish AT, Capecchi MR, Michalek JE, Zarzabal LA, Khan J, Yu Z, Parham DM, Barr FG, Meltzer PS, Chen Y, Keller C (2011) Evidence for an unanticipated relationship between undifferentiated pleomorphic sarcoma and embryonal rhabdomyosarcoma. Cancer Cell 19(2):177–191. doi:10.1016/j.ccr.2010.12.023

  • Scrable H, Witte D, Shimada H, Seemayer T, Sheng WW, Soukup S, Koufos A, Houghton P, Lampkin B, Cavenee W (1989) Molecular differential pathology of rhabdomyosarcoma. Genes Chromosom Cancer 1(1):23–35

    Article  PubMed  CAS  Google Scholar 

  • Sorensen PH, Lynch JC, Qualman SJ, Tirabosco R, Lim JF, Maurer HM, Bridge JA, Crist WM, Triche TJ, Barr FG (2002) PAX3-FKHR and PAX7-FKHR gene fusions are prognostic indicators in alveolar rhabdomyosarcoma: a report from the children’s oncology group. J Clin Oncol 20(11):2672–2679

    Article  PubMed  CAS  Google Scholar 

  • Sultan I, Qaddoumi I, Yaser S, Rodriguez-Galindo C, Ferrari A (2009) Comparing adult and pediatric rhabdomyosarcoma in the surveillance, epidemiology and end results program, 1973 to 2005: an analysis of 2,600 patients. J Clin Oncol 27(20):3391–3397. doi:10.1200/JCO.2008.19.7483

    Article  PubMed  Google Scholar 

  • Van Gaal JC, De Bont ES, Kaal SE, Versleijen-Jonkers Y, van der Graaf WT (2011) Building the bridge between rhabdomyosarcoma in children, adolescents and young adults: The road ahead. Crit Rev Oncol Hematol. doi:10.1016/j.critrevonc.2011.06.005

  • Williamson D, Missiaglia E, de Reynies A, Pierron G, Thuille B, Palenzuela G, Thway K, Orbach D, Lae M, Freneaux P, Pritchard-Jones K, Oberlin O, Shipley J, Delattre O (2010) Fusion gene-negative alveolar rhabdomyosarcoma is clinically and molecularly indistinguishable from embryonal rhabdomyosarcoma. J Clin Oncol 28(13):2151–2158

    Google Scholar 

  • Wolden SL, Alektiar KM (2010) Sarcomas across the age spectrum. Semin Radiat Oncol 20(1):45–51. doi:10.1016/j.semradonc.2009.09.003

    Google Scholar 

Download references

Acknowledgments

Institutional Physician-Scientist award (J.C.T.), NIH/NCI 1K23CA109060-05 (J.C.T.), Amschwand Sarcoma Cancer Foundation grant (J.C.T.), Nuovo-Soldati Foundation grant (S.N.D.), AstraZeneca France (S.N.D.) and Association pour la Recherche sur le Cancer (S.N.D.). This research is also supported in part by the National Institutes of Health through MD Anderson’s Cancer Center Support Grant CA016672.

Conflict of interest

We declare that we have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77054, USA

    Sarah N. Dumont & Robert S. Benjamin

  2. Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA

    Alexander J. Lazar

  3. Department of Pathology and Microbiology, University of Nebraska Medical Center, 989550 Nebraska Medical Center, Omaha, NE, 68198, USA

    Julia A. Bridge

  4. Sarcoma Center, Sylvester Comprehensive Cancer Center, 1475 NW 12th Avenue, Suite 3510, Miami, FL, 33136, USA

    Jonathan C. Trent

Authors
  1. Sarah N. Dumont
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alexander J. Lazar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Julia A. Bridge
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Robert S. Benjamin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jonathan C. Trent
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sarah N. Dumont.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dumont, S.N., Lazar, A.J., Bridge, J.A. et al. PAX3/7–FOXO1 fusion status in older rhabdomyosarcoma patient population by fluorescent in situ hybridization. J Cancer Res Clin Oncol 138, 213–220 (2012). https://doi.org/10.1007/s00432-011-1089-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-011-1089-7

Keywords

Search

Navigation