Pitfalls in immunohistochemical assessment of EGFR expression in soft tissue sarcomas.
BACKGROUND
New targeted cancer treatments acting against growth factor receptors such as the epidermal growth factor receptor (EGFR) necessitate selecting patients for treatment with these drugs. Besides carcinomas, soft tissue sarcomas (STS) express EGFR and might thereby be a promising target for this new therapeutic strategy.


OBJECTIVE
To test and compare different EGFR antibodies to determine the frequency of EGFR expression in STS.


METHODS
302 consecutive specimens of STS were examined using the tissue microarray technique. EGFR expression levels were assessed by immunohistochemistry using five different commercially available antibodies. Gene amplification status was measured by fluorescence in situ hybridisation (FISH). Immunoreactivity and amplification status were correlated with clinicopathological features and follow up data available in 163 cases.


RESULTS
EGFR expression frequency ranged between 0.3% and 52.9%, depending on the antibody and scoring method used. In all, 3.5% of the tumours showed egfr gene amplification by FISH, which correlated with EGFR expression for three antibodies. Only one antibody had independent prognostic value in multivariate analysis and correlated with an unfavourable outcome; egfr gene amplification status showed no correlation with clinical features.


CONCLUSIONS
Frequency of EGFR immunopositivity in STS strongly depends on the antibody used, and only one of five antibodies tested predicted an unfavourable clinical outcome. This indicates that choice of primary antibody and scoring system have a substantial impact on the determination of EGFR immunoreactivity.
Kersting
C
C
Institute of Pathology, University of Münster, Münster, Germany.
Packeisen
J
J
Leidinger
B
B
Brandt
B
B
von Wasielewski
R
R
Winkelmann
W
W
van Diest
P J
PJ
Gosheger
G
G
Buerger
H
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000276:immunology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D066246:ErbB Receptors / Q000276:immunology / Q000378:metabolism*; D005500:Follow-Up Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D011379:Prognosis; D012509:Sarcoma / Q000378:metabolism* / Q000473:pathology; D012983:Soft Tissue Neoplasms / Q000378:metabolism* / Q000473:pathology; D016019:Survival Analysis
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D066246:ErbB Receptors