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Genetic classification of STS

Prognostic value of myogenic differentiation in adult soft tissue sarcomas (STS) A study of 855 cases from the French Sarcoma Group. N Stock, MC Chateau, F Collin, L Guillou, A Leroux, B Marques, JJ Michels, D Ranchere, YM Robin, P Terrier, M Trassard, I Valo and JM Coindre.

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Genetic classification of STS

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  1. Prognostic value of myogenic differentiation in adult soft tissue sarcomas (STS)A study of 855 cases from the French Sarcoma Group N Stock, MC Chateau, F Collin, L Guillou, A Leroux, B Marques, JJ Michels, D Ranchere, YM Robin, P Terrier, M Trassard, I Valo and JM Coindre Department of Pathology, Institut Bergonié, Bordeaux, France and Pathology subgroup, French Sarcoma Group, France

  2. Genetic classificationof STS • Sarcomas with recurrent translocations • Sarcomas with oncogenic mutations • Sarcomas with simple genetic profile • Sarcomas with complex genetic profile

  3. Sarcomas with complex genetic profile • Leiomyosarcomas • Adult rhabdomyosarcomas • Pleomorphic liposarcomas • Myxofibrosarcomas • Poorly-differentiated sarcomas / MFH

  4. Sarcomas with complex genetic profile • Spindle cell / pleomorphic sarcomas • Difficult to classify • Prognosis and myogenic differentiation • Fletcher et al. J Clin Oncol 2001;19:3045-50 • Deyrup et al. Cancer 2003;98:805-13

  5. French Sarcoma Group Database • 2538 adult STS with primary event (January 2006) • STS with translocations: 785 (27.2%) • ALT/WDLPS and dedifferentiated LPS: 355 (12.3%) • MPNST, angioS, chondroS, osteoS,..: 401 (13.9%) • LMS, adult RMS, pleomorphic LPS, MFS and poorly-diff sarcomas/MFH: 1348 ( 46.7%)

  6. French Sarcoma Group DatabaseSarcomas with complex genetic profile • LMS, adult RMS, pleomorphic LPS, MFS and poorly-diff sarcomas/MFH: 1348 • 1002 with paraffin block directly available (biopsy and/or surgery in FSG centers) • 276 cases with frozen tissue for CGH-array and cDNA

  7. Sarcomas with complex genetic profileRe-classification - Methods • Pathology review (1002) • IHC on whole tissue sections (520):SMA, desmin, caldesmon, myogenin… • IHC on TMA (482):muscular markers, keratin, S100, CD34, MDM2, CDK4,…. • Fletcher et al, J Clin Oncol 2001;19:3045-50

  8. Sarcomas with complex genetic profileRe-classification - Results • 1002 cases: • 928 complex genetic profile sarcomas • 74 reclassified: 27 DDLPS, 47 others • 73 with metastasis at time of diagnosis and thus excluded for metastasis free survival study.

  9. Sarcomas with complex genetic profileRe-classification - Results Initial diagnosis (855) • LMS: 279 (32.6%) • Adult RMS: 23 • Pleomorphic LPS: 50 • MyxoFS: 32 (3.7%) • MFH: 471 (55%) • Final diagnosis (855) • LMS: 355 (41.5%) • Adult RMS: 28 • Pleomorphic LPS: 50 • MyxoFS: 128 (15%) • MFH: 294 (34.4%)

  10. Sarcomas with complex genetic profilePatients • Median age: 62 (15 - 98) • Sex: 447 M / 408 F • Locations: extremities 601 (70.3%), trunk wall 159 (18.6%), internal trunk 69 (8.1%), head and neck 26 (3%) • Deep tumors: 716 (83.7%) • Median size: 8 cm (1 - 30) • Median FU: 102 months • Distant metastasis: 296 (34.6%)

  11. Sarcomas with complex genetic profilePredictive factors for metastasis Univariate analysis • Grade: 3.1x10-8 • Myogenic differentiation: 4.7x10-7 • Internal trunk location: 1.4x10-4 • Tumor depth: 2.7x10-9 • Tumor size: 4.4x10-7

  12. Metastasis-free survival MyxoFS (n=128) MFH (n=294) LeiomyoS (n=355) P = 6.4 x 10-6

  13. Metastasis-free survival Myogenic differentiation Non-myogenic sarcomas (n=472) probability Myogenic sarcomas (n=383) P = 4.3 x 10-7 Time in months

  14. Metastasis-free survival Degree of differentiation MFH (n=294) Poorly D LeiomyoS (n=182) Well D LeiomyoS (n=172) P = 0.002

  15. Sarcomas with complex genetic profilePredictive factors for metastasis Multivariate analysis 1- Histological grade: x 4.65 2- Tumor depth: x 2.91 3- Myogenic differentiation: x 1.56 4- Internal trunk location: x1.52

  16. Complex genetic profile sarcomas excluding internal trunk n=626 Predictive factors for metastasis • Univariate analysis • Grade: 3.2x10-5 • Myogenic differentiation: 1.6x10-5 • Tumor size: 0.03 • Multivariate analysis • Histological grade: x 3.3 • Myogenic differentiation: x 1.44

  17. Sarcomas with complex genetic profileConclusions • Myogenic differentiation is an adverse prognostic factor • About 30% of sarcomas with complex genetic profiles are poorly differentiated and difficult to classify • Studies of genetic alterations should provide help for a more reproducible classification

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