High STEAP1 expression is associated with improved outcome of Ewing's sarcoma patients.
BACKGROUND
Ewing's sarcoma (ES) is the second most common bone or soft-tissue sarcoma in childhood and adolescence and features a high propensity to metastasize. The six-transmembrane epithelial antigen of the prostate 1 (STEAP1) is a membrane-bound mesenchymal stem cell marker highly expressed in ES. Here, we investigated the role of STEAP1 as an immunohistological marker for outcome prediction in patients with ES.


METHODS
Membranous STEAP1 immunoreactivity was analyzed using immunohistochemistry in 114 primary pre-chemotherapy ES of patients diagnosed from 1983 to 2010 and compared with clinical parameters and patient outcome. Median follow-up was 3.85 years (range 0.43-17.51).


RESULTS
A total of 62.3% of the ES samples displayed detectable STEAP1 expression with predominant localization of the protein at the plasma membrane. High membranous STEAP1 immunoreactivity was found in 53.5%, which correlated with better overall survival (P=0.021). Accordingly, no or low membranous STEAP1 expression was identified as an independent risk factor in multivariate analysis (hazard ratio 2.65, P=0.036).


CONCLUSIONS
High membranous STEAP1 expression predicts improved outcome and may help to define a specific subgroup of ES patients, who might benefit from adapted therapy regimens.
Children's Cancer Research and Roman Herzog Comprehensive Cancer Center, Laboratory of Functional Genomics and Transplantation Biology, Klinikum rechts der Isar, Technische Universität München, Munich; Medical Life Science and Technology Center, TUM Graduate School, Technische Universität München, Garching. Electronic address: thomas.gruenewald@lrz.tum.de.
T G P
TGP
Grunewald
Department of Pediatric Hematology and Oncology, University Hospital Münster, Münster.
A
A
Ranft
Institute of Pathology, Klinikum rechts der Isar, Technische Universität München, Munich; Institute of Pathology, Helmholtz-Zentrum München, Neuherberg, Germany.
I
I
Esposito
Institute of Pathology, Helmholtz-Zentrum München, Neuherberg, Germany.
P
P
da Silva-Buttkus
Institute of Pathology, Helmholtz-Zentrum München, Neuherberg, Germany.
M
M
Aichler
Bone Tumor Reference Center at the Institute of Pathology, University Hospital Basel, Basel, Switzerland.
D
D
Baumhoer
Institute of Pathology, Heinrich-Heine-University, Düsseldorf.
K L
KL
Schaefer
Institute of Pathology, Heinrich-Heine-University, Düsseldorf.
L
L
Ottaviano
Institute of Pathology, Heinrich-Heine-University, Düsseldorf; Center of Histopathology, Cytology, and Molecular Diagnostics (CHCMD), Trier, Germany.
C
C
Poremba
Bone Tumor Reference Center at the Institute of Pathology, University Hospital Basel, Basel, Switzerland.
G
G
Jundt
Department of Pediatric Hematology and Oncology, University Hospital Münster, Münster.
H
H
Jürgens
Department of Pediatric Hematology and Oncology, University Hospital Münster, Münster.
U
U
Dirksen
Children's Cancer Research and Roman Herzog Comprehensive Cancer Center, Laboratory of Functional Genomics and Transplantation Biology, Klinikum rechts der Isar, Technische Universität München, Munich.
G H S
GHS
Richter
Children's Cancer Research and Roman Herzog Comprehensive Cancer Center, Laboratory of Functional Genomics and Transplantation Biology, Klinikum rechts der Isar, Technische Universität München, Munich.
S
S
Burdach
D000293:Adolescent; D000328:Adult; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D002462:Cell Membrane / Q000201:enzymology / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010088:Oxidoreductases / Q000096:biosynthesis*; D012512:Sarcoma, Ewing / Q000201:enzymology / Q000276:immunology*; D055815:Young Adult
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D010088:Oxidoreductases; C432763:STEAP1 protein, human