Prognostic value of myogenic differentiation in adult soft tissue sarcomas (STS)
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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.

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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 l.jpg
Genetic classification tissue sarcomas (STS)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 l.jpg
Sarcomas with complex genetic profile tissue sarcomas (STS)

  • Leiomyosarcomas

  • Adult rhabdomyosarcomas

  • Pleomorphic liposarcomas

  • Myxofibrosarcomas

  • Poorly-differentiated sarcomas / MFH


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Sarcomas with complex genetic profile tissue sarcomas (STS)

  • 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


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French Sarcoma Group Database tissue sarcomas (STS)

  • 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 database sarcomas with complex genetic profile l.jpg
French Sarcoma Group Database tissue sarcomas (STS)Sarcomas 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


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Sarcomas with complex genetic profile tissue sarcomas (STS)Re-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


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Sarcomas with complex genetic profile tissue sarcomas (STS)Re-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.


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Sarcomas with complex genetic profile tissue sarcomas (STS)Re-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%)


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Sarcomas with complex genetic profile tissue sarcomas (STS)Patients

  • 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%)


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Sarcomas with complex genetic profile tissue sarcomas (STS)Predictive 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


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Metastasis-free survival tissue sarcomas (STS)

MyxoFS (n=128)

MFH (n=294)

LeiomyoS (n=355)

P = 6.4 x 10-6


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Metastasis-free survival tissue sarcomas (STS)

Myogenic differentiation

Non-myogenic sarcomas (n=472)

probability

Myogenic sarcomas (n=383)

P = 4.3 x 10-7

Time in months


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Metastasis-free survival tissue sarcomas (STS)

Degree of differentiation

MFH (n=294)

Poorly D LeiomyoS (n=182)

Well D LeiomyoS (n=172)

P = 0.002


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Sarcomas with complex genetic profile tissue sarcomas (STS)Predictive 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


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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


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Sarcomas with complex genetic profile n=626Conclusions

  • 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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