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BioMed Research International
Volume 2014 (2014), Article ID 367103, 9 pages
http://dx.doi.org/10.1155/2014/367103
Research Article

Molecular Profiling and Clinical Outcome of High-Grade Serous Ovarian Cancer Presenting with Low- versus High-Volume Ascites

1Division of Gynaecologic Oncology, Department of Obstetrics and Gynaecology, University of Toronto, Toronto, ON, Canada M5G 2M9
2Department of Obstetrics and Gynaecology, Trillium Health Partners, 2200 Eglinton Avenue West, Mississauga, ON, Canada L5M 2N1
3Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, ON, Canada M5G 2M9
4Department of Laboratory Medicine and Pathology, University Health Network, Toronto, ON, Canada M5T 2M9
5Princess Margaret Genomics Centre, University Health Network, Toronto, ON, Canada M5G 1L7
6Department of Laboratory Medicine and Pathology, Trillium Health Partners, Mississauga, ON, Canada L5M 2N1
7Hospital for Sick Children and Department of Immunology, University of Toronto, Toronto, ON, Canada M5G 1X8
8Division of Gynaecologic Oncology, Department of Obstetrics and Gynaecology, Princess Margaret Cancer Centre, Toronto, ON, Canada M5G 2M9
9Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, Toronto, ON, Canada M5T 3L9

Received 10 March 2014; Accepted 5 May 2014; Published 25 May 2014

Academic Editor: X. Li

Copyright © 2014 Tomer Feigenberg et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Epithelial ovarian cancer consists of multiple histotypes differing in etiology and clinical course. The most prevalent histotype is high-grade serous ovarian cancer (HGSOC), which often presents at an advanced stage frequently accompanied with high-volume ascites. While some studies suggest that ascites is associated with poor clinical outcome, most reports have not differentiated between histological subtypes or tumor grade. We compared genome-wide gene expression profiles from a discovery cohort of ten patients diagnosed with stages III-IV HGSOC with high-volume ascites and nine patients with low-volume ascites. An upregulation of immune response genes was detected in tumors from patients presenting with low-volume ascites relative to those with high-volume ascites. Immunohistochemical studies performed on tissue microarrays confirmed higher expression of proteins encoded by immune response genes and increased tumorinfiltrating cells in tumors associated with low-volume ascites. Comparison of 149 advanced-stage HGSOC cases with differential ascites volume at time of primary surgery indicated low-volume ascites correlated with better surgical outcome and longer overall survival. These findings suggest that advanced stage HGSOC presenting with low-volume ascites reflects a unique subgroup of HGSOC, which is associated with upregulation of immune related genes, more abundant tumor infiltrating cells and better clinical outcomes.