Molecular profiling and clinical outcome of high-grade serous ovarian cancer presenting with low- versus high-volume ascites.

Tomer Feigenberg,Anna Plotkin,Blaise Clarke,Michelle Letarte,Carl Virtanen,K Joan Murphy,Theodore J Brown,Marcus Q Bernardini,Alexandra Kollara,Barry Rosen

doi:10.1155/2014/367103

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.

Highlights

Epithelial ovarian cancer (EOC) is the leading cause of gynecologic cancer-related death in developed countries, with nearly a quarter million women diagnosed worldwide annually [1]
Recent large-scale gene expression studies identified at least four molecular subtypes within high-grade serous ovarian cancer (HGSOC) [4, 5], with some evidence associating these subtypes with differences in overall patient survival [4, 6]
The association of ascites with poor outcome in EOC could reflect the fact that HGSOC is an aggressive cancer that tends to present with high-volume ascites and carries poor prognosis compared to other histological subtypes and low-grade disease [8,9,10,11]

Summary

Introduction

Epithelial ovarian cancer (EOC) is the leading cause of gynecologic cancer-related death in developed countries, with nearly a quarter million women diagnosed worldwide annually [1]. The association of ascites with poor outcome in EOC could reflect the fact that HGSOC is an aggressive cancer that tends to present with high-volume ascites and carries poor prognosis compared to other histological subtypes and low-grade disease [8,9,10,11]. For this reason, we focused on a homogeneous group of patients diagnosed exclusively with HGSOC, to assess the significance of differences in ascites volume at the time of diagnosis. Ascites volume has not been captured as a parameter in molecular profiling studies

Methods

Results

Discussion

Conclusion