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Takuro Wada , O Sato, A Kawai, T Hasegawa Sapporo Medial University , Sapporo Japan PowerPoint Presentation
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Takuro Wada , O Sato, A Kawai, T Hasegawa Sapporo Medial University , Sapporo Japan

Takuro Wada , O Sato, A Kawai, T Hasegawa Sapporo Medial University , Sapporo Japan

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Takuro Wada , O Sato, A Kawai, T Hasegawa Sapporo Medial University , Sapporo Japan

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  1. Expression of EGFR, ERRB2, and KIT in Adult Soft Tissue Sarcomas:A Clinicopathological Study of 281 Cases Takuro Wada, O Sato, A Kawai, T Hasegawa Sapporo Medial University, Sapporo Japan National Cancer Center, Tokyo Japan

  2. Purpose • To analyze expression patterns of EGFR, ERBB2, and KIT on 281 patients with common adult STS by standard immunohistochemical technique on formalin-fixed, paraffin-embedded sections • To Verify whether a significant association with prognosis is present

  3. Patients • 281 adult patients with common soft tissue sarcomas in the extremities and trunk diagnosed and treated • at the NCC, Tokyo, Japan • Histologic subtype • Fibrosarcoma (FS) 11 • Leiomyosarcoma (LMS)11 • Myxoid liposarcoma (LSM)52 • Well differentiated liposarcoma(LSW)50 • MPNST18 • Myxofibrosarcoma (MFS)53 • Pleomorphic MFH (PMFH)44 • Synovial sarcoma (SS)42

  4. Characteristic of 281 patients • Gender: 152 females and 129 males • Age: 10 to 85 years (median 50 yrs) • Treatment: • Resection All patients • Radiotherapy 25 • Chemotherapy 37 • Chemo + Radi 23

  5. Pathology reviewing, grade and Staging • Tumor typing • WHO Classification of Soft Tissue Tumors • Histologic grade • Differentiation, necrosis, MIB-1 index • TNM staging classification

  6. Primary Antibodies

  7. Evaluation of staining Strength Distribution 3+ and>10% = Positive 2+ 1+ or ≤10%= Negative 0

  8. Results

  9. Immunohistochemical Pattern

  10. Immunohistochemical Pattern

  11. Diffuse EGFR (3+) in MPNST Diffuse EGFR (2+) in leiomyosarcoma

  12. Focal ERBB2 (2+) in epithelioid cells of biphasic synovial sarcoma Diffuse EGFR (3+) in spindle cells of biphasic synovial sarcoma

  13. Focal KIT (2+) in spindle cells of monophasic synovial sarcoma

  14. EGFR (-) 79% EGFR (+) 64%

  15. Variables associated with patient survival: Univariate analysis • Stage • Histological grade • Depth • Size • Positive EGFR staining

  16. Variables associated with patient survival: Multivariate analysis • Stage • Histological grade • Depth • Size • Positive EGFR staining

  17. Kaplan-Meier survival curves stratified by EGFR status and by tumor size EGFR- 1.0 1.0 EGFR- .8 .8 EGFR+ .6 .6 EGFR+ .4 .4 p=0.03 .2 p=0.06 .2 0.0 0.0 0 10 20 30 40 50 60 70 0 10 20 30 40 50 60 70 Size 5-10cm (n=135) Size>10cm (n=77)

  18. Kaplan-Meier survival curves stratified by EGFR status and by histological grade 1.0 EGFR+ 1.0 EGFR+ .8 .8 EGFR- .6 .6 EGFR- .4 .4 p=0.08 p=0.7 .2 .2 0.0 0.0 0 10 20 30 40 50 60 70 0 10 20 30 40 50 60 70 Grade 2 (n=74) Grade 3 (n=111)

  19. Discussion

  20. Expression of EGFR in STSs

  21. Expression of ERBB2 and KIT • Merimsky et al. (2002) • No overexpression of ERBB2 in 230 STSs • Hornick et al. (2002) • Very limited expression of KIT in 365 STSs • This study • Limited expression of ERBB2 and KIT

  22. EGFR (-) 79% EGFR (+) 64%

  23. Target-specific agents and approaches for anticancer therapy IMC-C225 ABX-EGF Tyrosine kinase inhibitor Irresa

  24. Conclusion • We analyzed the expression of EGFR, ERBB2, and KIT in 281 patients with STS • Positive staining of EGFR: 168/281 (60%) • Positive staining of ERBB2, KIT was limited • EGFR overexpression was a negative prognostic factor associated with histological grade