Journal
GYNECOLOGIC ONCOLOGY
Volume 152, Issue 2, Pages 368-374Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ygyno.2018.11.014
Keywords
High-grade serous ovarian cancer (HGSOC); Mesenchymal (MES); Stroma; Primary; Metastatic
Categories
Funding
- Mayo Clinic Specialized Program in Research Excellence (SPORE) [CA136393]
- Minnesota Ovarian Cancer Alliance (MOCA)
Ask authors/readers for more resources
Objective. Mesenchymal (MES) subtype of high-grade serous ovarian cancer (HGSOC) is associated with worse outcomes including survival and resectability compared with other molecular subtypes. Molecular subtypes have historically been derived from 'tumor', consisting of both cancer and stromal cells. We sought to determine the origins of multiple MES subtype gene signatures in HGSOC. Methods. Fifteen patients with MES subtype of HGSOC diagnosed between 2010 and 2013 were identified. Formalin-fixed paraffin-embedded (FFPE) blocks from primary surgery were sectioned for immunohistochemistry (IHC) staining of relevant proteins. Eight genes (ACTA2, COL5A1, COL11A1, FAP, POSTN, VCAN, ZEB1 and p-SMAD2) were selected for IHC staining based on their differential expression in MES vs. non-MES subtypes of HGSOC. Slides were scored for intensity and localization and simple statistics were used to compare expression results in cancer vs. stroma and between primary and metastatic sites. Results. COL5A1, VCAN, FAP, and ZEB1 proteins were almost exclusively expressed by stroma as opposed to cancer cells. In addition, stromal expression was dominant for ACTA2, COL11A1, POSTN and p-SMAD2. In general there were minimal differences in expression of proteins between primary and metastatic sites, exceptions being COL5A1 (reduced in metastases) and COL11A1 (increased in metastases). Nuclear p-SMAD2 expression was more common in metastatic stroma. Conclusions. The existing molecular classification of HGSOC MES subtype reflects a significant stromal contribution, suggesting an important role in HGSOC behavior and thus stroma may be a relevant therapeutic target. Specific patterns of expression indicate that collagens and TGF-beta signaling are involved in the metastatic process. (C) 2018 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available