The predictive potential of molecular detection in the nonmetastatic Ewing family of tumors.
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.
Department of Molecular Oncology, Felsenstein Medical Research Center, Petah-Tikva, Israel. savigad@post.tau.ac.il
Smadar
S
Avigad
Ian J
IJ
Cohen
Julia
J
Zilberstein
Ella
E
Liberzon
Yacov
Y
Goshen
Shifra
S
Ash
Isaac
I
Meller
Yehuda
Y
Kollender
Josephine
J
Issakov
Rina
R
Zaizov
Isaac
I
Yaniv
D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D001853:Bone Marrow / Q000473:pathology; D001859:Bone Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D017931:DNA Primers; D018572:Disease-Free Survival; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D008297:Male; D008967:Molecular Biology; D009360:Neoplastic Cells, Circulating; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D012494:Sampling Studies; D012512:Sarcoma, Ewing / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D017678:Sex Distribution; D016019:Survival Analysis; D014158:Transcription, Genetic
D017931:DNA Primers; D011993:Recombinant Fusion Proteins