Distinct Patterns of Stromal and Tumor Expression of ROR1 and ROR2 in Histological Subtypes of Epithelial Ovarian Cancer.
OBJECTIVE
The ROR1 and ROR2 receptor tyrosine kinases have both been implicated in ovarian cancer progression and have been shown to drive migration and invasion. There is an increasing importance of the role of stroma in ovarian cancer metastasis; however, neither ROR1 nor ROR2 expression in tumor or stromal cells has been analyzed in the same clinical cohort.


OBJECTIVE
To determine ROR1 and ROR2 expression in ovarian cancer and surrounding microenvironment and examine associations with clinicopathological characteristics.


METHODS
Immunohistochemistry for ROR1 and ROR2 was used to assess receptor expression in a cohort of epithelial ovarian cancer patients (n=178). Results were analyzed in relation to clinical and histopathological characteristics and survival. Matched patient sample case studies of normal, primary, and metastatic lesions were used to examine ROR expression in relation to ovarian cancer progression.


RESULTS
ROR1 and ROR2 are abnormally expressed in malignant ovarian epithelium and stroma. Higher ROR2 tumor expression was found in early-stage, low-grade endometrioid carcinomas. ROR2 stromal expression was highest in the serous subtype. In matched patient case studies, metastatic samples had higher expression of ROR2 in the stroma, and a recurrent sample had the highest expression of ROR2 in both tumor and stroma.


CONCLUSIONS
ROR1 and ROR2 are expressed in tumor-associated stroma in all histological subtypes of ovarian cancer and hold potential as therapeutic targets which may disrupt tumor and stroma interactions.
Metastasis Research Group, Lowy Cancer Research Centre and School of Women and Children's Health, Faculty of Medicine, University of New South Wales, Australia.
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Henry
Department of Gynaecological Oncology, Westmead Hospital and Centre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Australia.
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Emmanuel
South Eastern Area Laboratory Services Pathology, Prince of Wales Hospital Randwick, NSW, Australia.
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Lambie
South Eastern Area Laboratory Services Pathology, Prince of Wales Hospital Randwick, NSW, Australia.
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Loo
Prince of Wales Clinical School, Faculty of Medicine, University of New South Wales, Australia.
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Kan
Department of Gynaecological Oncology, Westmead Hospital and Centre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Australia.
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CJ
Kennedy
Department of Gynaecological Oncology, Westmead Hospital and Centre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Australia.
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de Fazio
Gynaecological Cancer Centre, Royal Hospital for Women, Sydney, Australia.
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Hacker
Metastasis Research Group, Lowy Cancer Research Centre and School of Women and Children's Health, Faculty of Medicine, University of New South Wales, Australia. Electronic address: caroline.ford@unsw.edu.au.
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Ford