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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. - PowerPoint PPT Presentation
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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
Genetic classification of STS
• Sarcomas with recurrent translocations
• Sarcomas with oncogenic mutations
• Sarcomas with simple genetic profile
• Sarcomas with complex genetic profile
Sarcomas with complex genetic profile
• Leiomyosarcomas
• Adult rhabdomyosarcomas
• Pleomorphic liposarcomas
• Myxofibrosarcomas
• Poorly-differentiated sarcomas / MFH
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
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%)
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
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
• 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.
Sarcomas with complex genetic profileRe-classification - Results
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%)
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%)
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
Metastasis-free survival
MyxoFS (n=128)
MFH (n=294)
LeiomyoS (n=355)
P = 6.4 x 10-6
Myogenic sarcomas (n=383)
P = 4.3 x 10-7
Time in months
pro
bab
ility
Metastasis-free survivalMyogenic differentiation
Non-myogenic sarcomas (n=472)
Metastasis-free survivalDegree of differentiation
Well D LeiomyoS (n=172)
Poorly D LeiomyoS (n=182)
MFH (n=294)
P = 0.002
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
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
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