ROR2 is a novel prognostic biomarker and a potential therapeutic target in leiomyosarcoma and gastrointestinal stromal tumour
Por:
Edris, B, Espinosa, I, Muhlenberg, T, Mikels, A, Lee, CH, Steigen, SE, Zhu, S, Montgomery, KD, Lazar, AJF, Lev, D, Fletcher, JA, Beck, AH, West, RB, Nusse, R, van de Rijn, M
Publicada:
1 jun 2012
Resumen:
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. Copyright (c) 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Filiaciones:
Edris, B:
Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA
Espinosa, I:
Hosp Santa Creu & Sant Pau, Inst Biomed Res, Dept Pathol, Barcelona, Spain
Muhlenberg, T:
Univ Essen Gesamthsch, Sch Med, W German Canc Ctr, Sarcoma Ctr, Essen, Germany
Mikels, A:
Stanford Univ, Dept Dev Biol, Sch Med, Stanford, CA 94305 USA
Stanford Univ, Howard Hughes Med Inst, Sch Med, Stanford, CA 94305 USA
Lee, CH:
Vancouver Gen Hosp, Dept Pathol, Vancouver, BC, Canada
Steigen, SE:
Univ Tromso, Dept Pathol, N-9001 Tromso, Norway
Lazar, AJF:
Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA
Lev, D:
Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA
Fletcher, JA:
Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA
Beck, AH:
Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA
Nusse, R:
Stanford Univ, Dept Dev Biol, Sch Med, Stanford, CA 94305 USA
Stanford Univ, Howard Hughes Med Inst, Sch Med, Stanford, CA 94305 USA
van de Rijn, M:
Stanford Univ, Med Ctr, Dept Pathol, Sch Med, Stanford, CA 94305 USA
Green Accepted
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