The predictive potential of molecular detection in the nonmetastatic Ewing family of tumors

Authors

  • Smadar Avigad Ph.D.,

    Corresponding author
    1. Department of Molecular Oncology, Felsenstein Medical Research Center, Petah–Tikva, Israel
    2. Department of Pediatric Hematology/Oncology, Schneider Children's Medical Center of Israel, Petah-Tikva, Israel
    • Department of Molecular Oncology, Schneider Children's Medical Center of Israel, Petah Tikva, 49202, Israel
    Search for more papers by this author
    • Fax: (011) 972 39253042

  • Ian J. Cohen M.B., Ch.B.,

    1. Department of Pediatric Hematology/Oncology, Schneider Children's Medical Center of Israel, Petah-Tikva, Israel
    Search for more papers by this author
  • Julia Zilberstein M.Sc.,

    1. Department of Molecular Oncology, Felsenstein Medical Research Center, Petah–Tikva, Israel
    Search for more papers by this author
  • Ella Liberzon M.Sc.,

    1. Department of Molecular Oncology, Felsenstein Medical Research Center, Petah–Tikva, Israel
    Search for more papers by this author
  • Yacov Goshen M.D.,

    1. Department of Pediatric Hematology/Oncology, Schneider Children's Medical Center of Israel, Petah-Tikva, Israel
    Search for more papers by this author
  • Shifra Ash M.D.,

    1. Department of Pediatric Hematology/Oncology, Schneider Children's Medical Center of Israel, Petah-Tikva, Israel
    Search for more papers by this author
  • Isaac Meller M.D.,

    1. Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
    Search for more papers by this author
  • Yehuda Kollender M.D.,

    1. Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
    Search for more papers by this author
  • Josephine Issakov M.D.,

    1. Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
    Search for more papers by this author
  • Rina Zaizov M.D.,

    1. Department of Molecular Oncology, Felsenstein Medical Research Center, Petah–Tikva, Israel
    2. Department of Pediatric Hematology/Oncology, Schneider Children's Medical Center of Israel, Petah-Tikva, Israel
    Search for more papers by this author
  • Isaac Yaniv M.D.

    1. Department of Molecular Oncology, Felsenstein Medical Research Center, Petah–Tikva, Israel
    2. Department of Pediatric Hematology/Oncology, Schneider Children's Medical Center of Israel, Petah-Tikva, Israel
    Search for more papers by this author

Abstract

BACKGROUND

Tumors in the Ewing family (EFTs) are the second most common bone tumors in children and adolescents. Despite aggressive chemotherapy, one-third of patients with localized tumor still may develop recurrences. This implies that not all tumor cells are eradicated and that the patients may have a level of residual disease. EFTs are characterized by specific chromosomal translocations that result in chimeric transcripts that can be detected with reverse transcriptase-polymerase chain reaction (RT-PCR) analysis.

METHODS

The authors report the prognostic potential of the positive chimeric transcript (EWS/FLI1) in bone marrow (BM) and/or peripheral blood (PBL) in 26 patients with EFT during a long follow-up period (median, 61 months).

RESULTS

At diagnosis, 43% of patients had positive RT-PCR BM results, with no correlation to tumor progression (P = 0.3). During follow-up, 58% of patients had positive RT-PCR results in their last sample analyzed (BM and/or PBL). A highly significant correlation between the presence of the chimeric transcript and disease progression was detected (P = 0.0028). In a multivariate analysis, the percentage of tumor necrosis (P = 0.007) and RT-PCR results during follow-up (P = 0.02) remained significant prognostic markers. In 10 of 11 patients who developed disease progression, BM and/or PBL samples were positive for the chimeric transcript before evidence of overt clinical recurrence.

CONCLUSIONS

Occult tumor cells in BM and/or PBL samples during long follow-up are strong predictors of recurrent disease in patients with nonmetastatic EFTs. Cancer 2004;100:1053–8. © 2004 American Cancer Society.

Ancillary