title: Molecular profiling and clinical outcome of high-grade serous ovarian cancer presenting with low- versus high-volume ascites.
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.
authors: Division of Gynaecologic Oncology, Department of Obstetrics and Gynaecology, University of Toronto, Toronto, ON, Canada M5G 2M9 ; Department of Obstetrics and Gynaecology, Trillium Health Partners, 2200 Eglinton Avenue West, Mississauga, ON, Canada L5M 2N1.
authors: Tomer
authors: 0000-0003-3773-0018
authors: T
authors: Feigenberg
authors: Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, ON, Canada M5G 2M9 ; Department of Laboratory Medicine and Pathology, University Health Network, Toronto, ON, Canada M5T 2M9.
authors: Blaise
authors: B
authors: Clarke
authors: Princess Margaret Genomics Centre, University Health Network, Toronto, ON, Canada M5G 1L7.
authors: Carl
authors: C
authors: Virtanen
authors: Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, ON, Canada M5G 2M9 ; Department of Laboratory Medicine and Pathology, Trillium Health Partners, Mississauga, ON, Canada L5M 2N1.
authors: Anna
authors: A
authors: Plotkin
authors: Hospital for Sick Children and Department of Immunology, University of Toronto, Toronto, ON, Canada M5G 1X8.
authors: Michelle
authors: 0000-0002-5901-7582
authors: M
authors: Letarte
authors: Division of Gynaecologic Oncology, Department of Obstetrics and Gynaecology, University of Toronto, Toronto, ON, Canada M5G 2M9 ; Division of Gynaecologic Oncology, Department of Obstetrics and Gynaecology, Princess Margaret Cancer Centre, Toronto, ON, Canada M5G 2M9.
authors: Barry
authors: B
authors: Rosen
authors: Division of Gynaecologic Oncology, Department of Obstetrics and Gynaecology, University of Toronto, Toronto, ON, Canada M5G 2M9 ; Division of Gynaecologic Oncology, Department of Obstetrics and Gynaecology, Princess Margaret Cancer Centre, Toronto, ON, Canada M5G 2M9.
authors: Marcus Q
authors: MQ
authors: Bernardini
authors: Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, Toronto, ON, Canada M5T 3L9.
authors: Alexandra
authors: 0000-0002-6786-9582
authors: A
authors: Kollara
authors: Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, Toronto, ON, Canada M5T 3L9.
authors: Theodore J
authors: TJ
authors: Brown
authors: Division of Gynaecologic Oncology, Department of Obstetrics and Gynaecology, University of Toronto, Toronto, ON, Canada M5G 2M9 ; Division of Gynaecologic Oncology, Department of Obstetrics and Gynaecology, Princess Margaret Cancer Centre, Toronto, ON, Canada M5G 2M9.
authors: K Joan
authors: KJ
authors: Murphy
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001201:Ascites / Q000235:genetics* / Q000473:pathology*; D000077216:Carcinoma, Ovarian Epithelial; D018284:Cystadenocarcinoma, Serous / Q000235:genetics* / Q000276:immunology / Q000473:pathology* / Q000601:surgery; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D063990:Gene Ontology; D006801:Humans; D007109:Immunity; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000276:immunology / Q000473:pathology* / Q000601:surgery; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology* / Q000601:surgery; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D009363:Neoplasm Proteins