Markers of fibroblast-rich tumor stroma and perivascular cells in serous ovarian cancer: Inter- and intra-patient heterogeneity and impact on survival
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Sara Corvigno1, G. Bea A. Wisman3, Artur Mezheyeuski1, Ate G.J. van der Zee3, Hans W. Nijman3, Elisabeth Åvall-Lundqvist1,4, Arne Östman1, Hanna Dahlstrand1,2
1Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
2Unit for Breast, Gynecologic Cancer and Sarcoma, Department of Oncology, Karolinska University Hospital, Stockholm, Sweden
3Department of Gynecologic Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
4Department of Oncology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
Hanna Dahlstrand, email: firstname.lastname@example.org
Keywords: serous ovarian cancer, tumor microenvironment, cancer associated fibroblasts, pericytes, prognosis
Received: August 20, 2015 Accepted: February 11, 2016 Published: February 23, 2016
Inter- and intra-patient variations in tumor microenvironment of serous ovarian cancer are largely unexplored. We aimed to explore potential co-regulation of tumor stroma characteristics, analyze their concordance in primary and metastatic lesions, and study their impact on survival. A tissue microarray (TMA) with 186 tumors and 91 matched metastases was subjected to immunohistochemistry double staining with endothelial cell marker CD34 and fibroblast and pericyte markers α-SMA, PDGFβR and desmin. Images were digitally analyzed to yield “metrics” related to vasculature and stroma features.
Intra-case analyses showed that PDGFβR in perivascular cells and fibroblasts were strongly correlated. Similar findings were observed concerning α-SMA. Most stroma characteristics showed large variations in intra-case comparisons of primary tumors and metastasis. Large PDGFβR-positive stroma fraction and high PDGFβFR positive perivascular intensity were both significantly associated with shorter survival in uni- and multi-variate analyses (HR 1.7, 95% CI 1.1-2.5; HR 1.7, 95% CI 1.1-2.8).
In conclusion, we found PDGFβR- and α-SMA-expression to be largely independent of each other but concordantly activated in perivascular cells and in fibroblasts within the primary tumor. Stromal characteristics differed between primary tumors and metastases. PDGFβR in perivascular cells and in fibroblasts may be novel prognostic markers in serous ovarian cancer.
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