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

Badreddin Edris, Iñigo Espinosa, Thomas Mühlenberg, Amanda Mikels, Cheng Han Lee, Sonja E. Steigen, Shirley Zhu, Kelli D. Montgomery, Alexander J.F. Lazar, Dina Lev, Jonathan A. Fletcher, Andrew H. Beck, Robert B. West, Roel Nusse, Matt Van De Rijn

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)223-233
Number of pages11
JournalJournal of Pathology
Volume227
Issue number2
DOIs
StatePublished - Jun 2012
Externally publishedYes

Keywords

  • gastrointestinal stromal tumour
  • leiomyosarcoma
  • receptor tyrosine kinases
  • ROR2

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