Skip to main content

Molecular Genetic Detection of Minimal Metastatic and Residual Disease in Ewing’s Tumors

  • Chapter
Transplantation in Hematology and Oncology

Summary

EWS/ets-oncogene fusions that result from the rearrangement of chromosome 22 observed in Ewing’s tumors (ET) provide tumor-specific markers that can be used to detect contaminating tumor cells in bone marrow (BM) and peripheral blood (PB) samples by means of a highly sensitive reverse-transcriptase-polymerase chain reaction technique (RT-PCR). We analyzed BM samples obtained from 59 ET patients at diagnosis. Additional PB samples from 15 patients were available for RT-PCR. Median observation time of 42 ET patients was long enough to calculate overall and event-free survival curves according to the presence or absence of tumor cells in BM as detected by RT-PCR.

At diagnosis, 49% of ET patients had BM positivity detected by RT-PCR (32% in clinically localized and 72% in metastatic ET patients, respecively). No correlation with clinical parameters such as size, localization, histology, or type of fusion transcript of the tumor was found. BM positivity was associated with the presence of clinically metastatic disease and a statistically significant unfavorable outcome in univariate analysis. In contrast, the overall and eventfree survival of 24 ET patients with localized disease did not reveal statistically significant differences between the presence or absence of RT-PCR detected tumor cells in BM. PB samples from non-metastatic ET patients were negative and circulating tumor. cells were detected in only 50% of clinically metastatic patients.

These results suggest that BM is a more appropriate target for the detection of occult tumor cells than PB. However, to date RT-PCR detected BM contamination cannot be considered to be an established risk factor in staging procedures. Further studies are needed to appreciate the relationship and independence of BM positivity in ET patients.

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
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight 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

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Burdach, S., Jürgens, H., Peters, C., Nürnberger, W., Mauz Korholz, C., Korholz, D., Paulussen, M., Pape, H., Dilloo, D., Koscielniak, E., and et al (1993). Myeloablative radiochemotherapy and hematopoietic stem-cell rescue in poor-prognosis Ewing’s sarcoma. J. Clin. Oncol. 11, 1482–1488

    PubMed  CAS  Google Scholar 

  • Cangir, A., Vietti, T.J., Gehan, E.A., Burgert, E.O., Jr., Thomas, P., Tefft, M., Nesbit, M.E., Kissane, J., and Pritchard, D. (1990). Ewing’s sarcoma metastatic at diagnosis. Results and comparisons of two intergroup Ewing’s sarcoma studies. Cancer 66, 887–893

    Article  PubMed  CAS  Google Scholar 

  • Delattre, O., Zucman, J., Melot, T., Garau, X.S., Zucker, J.M., Lenoir, G.M., Ambros, P.F., Sheer, D., Turc Carel, C., Triche, T. J., and et al (1994). The Ewing family of tumors—a subgroup of small-round-cell tumors defined by specific chimeric transcripts [see comments]. N. Engl. J. Med. 331, 294–299

    Article  PubMed  CAS  Google Scholar 

  • Delattre, O., Zucman, J., Plougastel, B., Desmaze, C., Melot, T., Peter, M., Kovar, H., Joubert, I., de Jong, P., Rouleau, G., and et al (1992). Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours. Nature 359, 162–165

    Article  PubMed  CAS  Google Scholar 

  • Dockhorn Dworniczak, B., Schafer, K.L., Blasius, S., Christiansen, H., Koscielniak, E., Ritter, J., Winkelmann, W., Jurgens, H., and Bocker, W. (1997). Assessment of molecular genetic detection of chromosome translocations in the differential diagnosis of pediatric sarcomas. Klin. Padiatr. 209, 156–164

    Article  PubMed  CAS  Google Scholar 

  • Dockhorn Dworniczak, B., Schafer, K.L., Dantcheva, R., Blasius, S., Winkelmann, W., Strehl, S., Burdach, S., van Valen, F., Jurgens, H., and Bocker, W. (1994). Diagnostic value of the molecular genetic detection of the t(11; 22) translocation in Ewing’s tumours. Virchows Arch. 425; 107–112

    Article  PubMed  CAS  Google Scholar 

  • Fagnou, C., Michon, J., Peter, M., Bernoux, A., Oberlin, O., Zucker, J.M., Magdelenat, H., and Delattre, O. (1998). Presence of tumor cells in bone marrow but not in blood is associated with adverse prognosis in patients with Ewing’s tumor. Societe Francaise d’Oncologie Pediatrique. J Clin Oncol 16, 1707–1711

    PubMed  CAS  Google Scholar 

  • Grohs, J.G., Zoubek, A., Jugovic, D., Hartmann, T., Lang, S., Gadner, H., Kovar, H., and Windhager, R. (1996). Mobilisation of tumor cells during surgery in patients with Ewing tumor. Med. Pediatr. Oncol. 27, 256

    Google Scholar 

  • Hirsch Ginsberg, C. (1998). Detection of minimal residual disease: relevance for diagnosis and treatment of human malignancies. Annu. Rev. Med.49.

    Google Scholar 

  • Horowitz, M.E., Malawer, M.M., and Woo, S.Y. (1997). Ewing’s sarcoma family of tumors: Ewing’s sarcoma of bone and soft tissue and the peripheral primitive neuroectodermal tumors. In Principals and Practice of Pediatric Oncology. P. A. Pizzo and D.G. Poplack, eds. (Philadelphia, PA: pp. 831–864

    Google Scholar 

  • Jeon, I.S., Davis, J.N., Braun, B.S., Sublett, J.E., Roussel, M.F., Denny, C.T., and Shapiro, D.N. (1995). A variant Ewing’s sarcoma translocation (7522) fuses the EWS gene to the ETS gene ETV1. Oncogene 10, 1229–1234

    PubMed  CAS  Google Scholar 

  • Jurgens, H., Exner, U., Gadner, H., Harms, D., Michaelis, J., Sauer, R., Treuner, J., Voute, T., Winkelmann, W., Winkler, K., and et al (1988). Multidisciplinary treatment of primary Ewing’s sarcoma of bone. A 6-year experience of a European Cooperative Trial. Cancer 61, 23–32

    Article  PubMed  CAS  Google Scholar 

  • Kelly, K.M., Womer, R.B., and Barr, F.G. (1996). Minimal disease detection in patients with alveolar rhabdomyosarcoma using a reverse transcriptase-polymerase chain reaction method. Cancer 78, 1320–1327

    Article  PubMed  CAS  Google Scholar 

  • Ladanyi, M. (1995). The emerging molecular genetics of sarcoma translocations. Diagn. Mol. Pathol. 4, 162–173

    Article  PubMed  CAS  Google Scholar 

  • Oberlin, O., Bayle, C., Hartmann, O., Terrier Lacombe, M.J., and Lemerle, J. (1995). Incidence of bone marrow involvement in Ewing’s sarcoma: value of extensive investigation of the bone marrow. Med. Pediatr. Oncol. 24, 343–346

    Article  PubMed  CAS  Google Scholar 

  • Pantel, K. (1996). Detection of minimal disease in patients with solid tumors. J. Hematother.5, 359–367

    Article  PubMed  CAS  Google Scholar 

  • Peter, M., Couturier, J., Pacquement, H., Michon, J., Thomas, G., Magdelenat, H., and Delattre, O. (1997). A new member of the ETS family fused to EWS in Ewing tumors. Oncogene 14, 1159–1164

    Article  PubMed  CAS  Google Scholar 

  • Peter, M., Magdelenat, H., Michon, J., Melot, T., Oberlin, O., Zucker, J.M., Thomas, G., and Delattre, O. (1995). Sensitive detection of occult Ewing’s cells by the reverse transcriptase-polymerase chain reaction. Br. J. Cancer 72, 96–100

    Article  PubMed  CAS  Google Scholar 

  • Pfleiderer, C., Zoubek, A., Gruber, B., Kronberger, M., Ambros, P.F., Lion, T., Fink, F.M., Gadner, H., and Kovar, H. (1995). Detection of tumour cells in peripheral blood and bone marrow from Ewing tumour patients by RT-PCR. Int. J. Cancer 64, 135–139

    Article  PubMed  CAS  Google Scholar 

  • Ross, A.A. (1998). Minimal residual disease in solid tumor malignancies: a review. J Hematother 7, 9–18

    Article  PubMed  CAS  Google Scholar 

  • Sorensen, P.H., Lessnick, S.L., Lopez Terrada, D., Liu, X.F., Triche, T.J., and Denny, C.T. (1994). A second Ewing’s sarcoma translocation, t(21;22), fuses the EWS gene to another ETS-family transcription factor, ERG. Nat. Genet. 6, 146–151

    Article  PubMed  CAS  Google Scholar 

  • Toretsky, J.A., Neckers, L., and Wexler, L.H. (1995). Detection of (n;22)(q24;qi2) translocation-bearing cells in peripheral blood progenitor cells of patients with Ewing’s sarcoma family of tumors. J. Natl. Cancer Inst. 87, 385–386

    Article  PubMed  CAS  Google Scholar 

  • Urano, F., Umezawa, A., Hong, W., Kikuchi, H., and Hata, J. (1996). A novel chimera gene between EWS and E1A-F, encoding the adenovirus E1A enhancer-binding protein, in extraosseous Ewing’s sarcoma. Biochem. Biophys. Res. Commun. 219, 608–612

    Article  PubMed  CAS  Google Scholar 

  • West, D.C., Grier, H.E., Swallow, M.M., Demetri, G.D., Granowetter, L., and Sklar, J. (1997). Detection of circulating tumor cells in patients with Ewing’s sarcoma and peripheral primitive neuroectodermal tumor. J. Clin. Oncol. 15, 583–588

    PubMed  CAS  Google Scholar 

  • Zoubek, A., Dockhorn Dworniczak, B., Delattre, O., Christiansen, H., Niggli, F., Gatterer Menz, I., Smith, T.L., Jurgens, H., Gadner, H., and Kovar, H. (1996). Does expression of different EWS chimeric transcripts define clinically distinct risk groups of Ewing tumor patients? J. Clin. Oncol. 14, 1245–1251

    PubMed  CAS  Google Scholar 

  • Zoubek, A., Kovar, H., Kronberger, M., Amann, G., Windhager, R., Gruber, B., and Gadner, H. (1996). Mobilization of tumour cells during biopsy in an infant with Ewing sarcoma. Eur. J. Pediatr. 155, 373–376

    Article  PubMed  CAS  Google Scholar 

  • Zoubek, A., Ladenstein, R., Windhager, R., Amann, G., Fischmeister, G., Kager, L., Jugovic, D., Ambros, P.F., Gadner, H., and Kovar, H. (1998). Predictive potential of testing for bone marrow involvesment in Ewing tumor patients by RT-PCR: a preliminary evaluation. Int. J. Cancer 79, 56–60

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Dockhorn-Dworniczak, B. et al. (2000). Molecular Genetic Detection of Minimal Metastatic and Residual Disease in Ewing’s Tumors. In: Berdel, W.E., et al. Transplantation in Hematology and Oncology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-59592-9_21

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-59592-9_21

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-64041-4

  • Online ISBN: 978-3-642-59592-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics