Article

ROR2 is a novel prognostic biomarker and a potential therapeutic target in leiomyosarcoma and gastrointestinal stromal tumour.

Department of Pathology, Stanford University School of Medicine, CA, USA.
The Journal of Pathology (impact factor: 6.32). 01/2012; 227(2):223-33. DOI:10.1002/path.3986
Source: PubMed

ABSTRACT Soft-tissue sarcomas are a group of malignant tumours whose clinical management is complicated by morphological heterogeneity, inadequate molecular markers and limited therapeutic options. Receptor tyrosine kinases (RTKs) have been shown to play important roles in cancer, both as therapeutic targets and as prognostic biomarkers. An initial screen of gene expression data for 48 RTKs in 148 sarcomas showed that ROR2 was expressed in a subset of leiomyosarcoma (LMS), gastrointestinal stromal tumour (GIST) and desmoid-type fibromatosis (DTF). This was further confirmed by immunohistochemistry (IHC) on 573 tissue samples from 59 sarcoma tumour types. Here we provide evidence that ROR2 expression plays a role in the invasive abilities of LMS and GIST cells in vitro. We also show that knockdown of ROR2 significantly reduces tumour mass in vivo using a xenotransplantation model of LMS. Lastly, we show that ROR2 expression, as measured by IHC, predicts poor clinical outcome in patients with LMS and GIST, although it was not independent of other clinico-pathological features in a multivariate analysis, and that ROR2 expression is maintained between primary tumours and their metastases. Together, these results show that ROR2 is a useful prognostic indicator in the clinical management of these soft-tissue sarcomas and may represent a novel therapeutic target.

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Keywords

573 tissue samples
 
clinical management
 
desmoid-type fibromatosis
 
gastrointestinal stromal tumour
 
gene expression data
 
inadequate molecular markers
 
invasive abilities
 
limited therapeutic options
 
malignant tumours
 
morphological heterogeneity
 
multivariate analysis
 
novel therapeutic target
 
poor clinical outcome
 
prognostic biomarkers
 
Receptor tyrosine kinases
 
roles
 
ROR2 expression
 
soft-tissue sarcomas
 
therapeutic targets
 
useful prognostic indicator