expression of egfr, errb2, and kit in adult soft tissue sarcomas: a clinicopathological study of 281...
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Expression of EGFR, ERRB2, and Expression of EGFR, ERRB2, and KIT in Adult Soft Tissue Sarcomas:KIT in Adult Soft Tissue Sarcomas:
A Clinicopathological Study of 281 CasesA Clinicopathological Study of 281 Cases
Takuro Wada, O Sato, A Kawai, T HasegawaSapporo Medial University, Sapporo JapanNational Cancer Center, Tokyo Japan
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
Patients
281 adult patients with common soft tissue sarcomas in the extremities and trunk diagnosed and treated at the NCC, Tokyo, Japan
Histologic subtypeFibrosarcoma (FS) 11Leiomyosarcoma (LMS) 11 Myxoid liposarcoma ( LSM) 52Well differentiated liposarcoma ( LSW) 50MPNST 18Myxofibrosarcoma (MFS) 53Pleomorphic MFH (PMFH) 44Synovial sarcoma (SS) 42
Characteristic of 281 patients
Gender: 152 females and 129 males Age: 10 to 85 years (median 50 yrs) Treatment:
Resection All patientsRadiotherapy 25Chemotherapy 37Chemo + Radi 23
Pathology reviewing, grade and Staging Tumor typing
WHO Classification of Soft Tissue Tumors Histologic grade
Differentiation, necrosis, MIB-1 index TNM staging classification
Primary Antibodies
Antibody Source Dilution Positive control
EGFR, mouse monoclonal
DakoCytomation,
Clone 2-18C9
Prediluted Breast ca
ERBB2, rabbit polyclonal
DakoCytomation 1:500 Breast ca
KIT, rabbit polyclonal
DakoCytomation 1:50 Mast cell
0
1+or ≤ 10% = Negative
2+
3+and >10% = Positive
Strength Distribution
Evaluation of staining
Results
Immunohistochemical Pattern
Histologic type No. EGFR
Fibrosarcoma 11 4 (36%)
Leiomyosarcoma 11 8 (73%)
Myxoid liposarcoma 52 3 (6%)
Well-D liposarcoma 50 19 (38%)
Myxofibrosarcoma 53 16 (89%)
MPNST 18 47 (89%)
PMFH 44 39 (89%)
Synovial sarcoma 42 32 (76%)
Total 281 168 (60%)
Immunohistochemical Pattern
Histologic type No. EGFR ERBB2 KIT
Fibrosarcoma 11 4 (36%) 0 0
Leiomyosarcoma 11 8 (73%) 0 0
Myxoid liposarcoma 52 3 (6%) 0 0
Well-D liposarcoma 50 19 (38%) 0 0
Myxofibrosarcoma 53 16 (89%) 0 0
MPNST 18 47 (89%) 0 0
PMFH 44 39 (89%) 0 0
Synovial sarcoma 42 32 (76%) 3 2
Total 281 168 (60%) 3 2
Diffuse EGFR (2+) in leiomyosarcoma
Diffuse EGFR (3+) in MPNST
Diffuse EGFR (3+) in spindle cells of biphasic synovial sarcoma
Focal ERBB2 (2+) in epithelioid cells of biphasic synovial sarcoma
Focal KIT (2+) in spindle cells of monophasic synovial sarcoma
Overall survival curves for EGFR
N=281 P=0.03
month
706050403020100
Ove
rall
surv
ival
1.0
.8
.6
.4
.2
0.0
EGFR (+)
EGFR (-)79%
64%
Variables associated with patient survival: Univariate analysis Stage Histological grade Depth Size Positive EGFR staining
Variables associated with patient survival: Multivariate analysis Stage Histological grade Depth Size Positive EGFR staining
706050403020100
1.0
.8
.6
.4
.2
0.0706050403020100
1.0
.8
.6
.4
.2
0.0
Kaplan-Meier survival curves stratified by EGFR status and by tumor size
Size 5-10cm (n=135) Size>10cm (n=77)
EGFR-EGFR-
EGFR+
EGFR+
p=0.03 p=0.06
706050403020100
1.0
.8
.6
.4
.2
0.0706050403020100
1.0
.8
.6
.4
.2
0.0
Kaplan-Meier survival curves stratified by EGFR status and by histological grade
Grade 2 (n=74) Grade 3 (n=111)
EGFR-
EGFR-
EGFR+
EGFR+
p=0.08 p=0.7
Discussion
Expression of EGFR in STSs
Authors Cases Positive Subtype
Gusterson et al. (1985) 35 18 (51%) MFH, SS, Epi
Perosio et al. (1989) 40 20 (50%)
Duda et al. (1993) 43 21(49%)
Barbashina (2002) 19 13 (68%) SS
Nielsen (2002) 42 18 (52%) SS
This study 281 170 (60%)
MFH, SS, MPNST
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 studyLimited expression of ERBB2 and KIT
Overall survival curves for EGFR
N=281 P=0.03
month
706050403020100
Ove
rall
surv
ival
1.0
.8
.6
.4
.2
0.0
EGFR (+)
EGFR (-)79%
64%
IMC-C225ABX-EGFTyrosine kinase inhibitor
Irresa
Target-specific agents and approaches for anticancer therapy
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