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BIOLOGICAL MARKERS OF PROGNOSIS IN EWING'S SARCOMA: THE ROLE OF GAL3BP

BIOLOGICAL MARKERS OF PROGNOSIS IN EWING'S SARCOMA: THE ROLE OF GAL3BP. Katia Scotlandi, Diana Zambelli, Monia Zuntini, and Piero Picci Istituti Ortopedici Rizzoli Bologna, Italy. CTOS meeting, Seattle 2007. MDR transfectants. TC-71. Drug resistant cells.

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BIOLOGICAL MARKERS OF PROGNOSIS IN EWING'S SARCOMA: THE ROLE OF GAL3BP

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  1. BIOLOGICAL MARKERS OF PROGNOSIS IN EWING'S SARCOMA: THE ROLE OF GAL3BP Katia Scotlandi, Diana Zambelli, Monia Zuntini, and Piero Picci Istituti Ortopedici Rizzoli Bologna, Italy CTOS meeting, Seattle 2007

  2. MDR transfectants TC-71 Drug resistant cells From experimental models to clinics • 4 different variants, characterized by: • MDR phenotype • Loss of malignancy

  3. Gene expression profile of these cells COMMON UP-REGULATED GENES

  4. gene functional Networks operating in the regulation of mets capabilities

  5. Validation by TaqMAN Real Time PCR array Genes: CDC42EP1, CTGF, FVT1, IRS1 LGALS3BP HINT IFITM2, STOML2 RPS4Y1 CANX CTGF KPNA2 RNP24

  6. Comparison of the mean expression values of primary lesions with recurrences or metastases for each gene did not provide significant results. However remarkable reduction in the recurrences and metastasis groups was observed for some genes

  7. p = 0.04 H L p = 0.03 p = 0.04 H H L L Prognostic Value of 6 out of 12 genes EFS OVS RPS4Y1 IFITM2

  8. p = 0.03 H L p = 0.06 H p = 0.03 H L L p = 0.06 H L Prognostic Value EFS OVS HINT1 STOML2

  9. EFS OVS p = 0.005 H LGALS3BP L p = 0.008 H L Prognostic Value None of these 6 prognostic genes displayed correlation with clinical pathological features. However, GALS3BP status showed a statistically significant, positive correlation with the fusion type translocation (p= 0.0007, Fisher’s exact test), EWS/Fli-1 type 1 fusion occurring more frequently in LGALS3BP high-expressing cases (17/20, 85% vs 7/22, 32%)

  10. Prognostic Value As expected, EWS/Fli-1 type 1 expression also showed significant correlation with survival

  11. Prognostic Value:Multivariate Analysis Event-Free Survival Overall Survival

  12. Evaluation of Protein Expression by Tissue Array Analysis In collaboration with A.Llombart-Bosch, University of Valencia, Spain

  13. 39 LOW 21 HIGH EFS OVS H H L L p = 0.03 p = 0.03 Prognostic Value:LGALS3BP Protein Expression (Monia Zuntini1*, Diana Zambelli1*, Filippo Nardi1, Maria Cristina Manara1, Massimo Serra1, Stefano Ferrari2, Patrizia Bacchini3, Antonio Llombart-Bosch4, Stefano Iacobelli5, Piero Picci1, and Katia Scotlandi1Biological indicators of prognosis in Ewing’s sarcoma: an emerging role for lectin galactoside-binding soluble 3 binding protein (LGALS3BP) (Submitted to JCO))

  14. GAL3-BP • LGALS3BP (also known as 90K or Mac-2 binding protein) was originally identified as a tumor-associated antigen in breast cancer • It binds galectins and appears to be have a role in cell-cell adhesion • A dualistic role depending on the cellular context • In EWS, high expression is associated with better prognosis • Molecular mechanisms?? Studies are in progress

  15. LGALS3BP/90K in EWS cell lines mRNA Protein

  16. TC/90K CLONES Screening of 90 clones by ELISA 20 CLONES

  17. Future plans • Analyze the presence of 90K in the serum of EWS patients • Evaluate the biological behavior of TC/90K clones • Growth ability, both in monolayer and soft-agar • Adhesion to different substrates • Migration and invasion processes • Chemo sensitivity to drugs commonly applied in the treatment of EWS patients

  18. Thanks to: EU project EUROBONET AIRC Regione Emilia Romagna and Italian Ministry of Health

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