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

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