title: Comparative transcriptome analysis links distinct peritoneal tumor spread types, miliary and non-miliary, with putative origin, tubes and ovaries, in high grade serous ovarian cancer.
abstract: High grade serous ovarian cancer (HGSOC) is characterized by extensive local, i.e. peritoneal, tumor spread, manifested in two different clinical presentations, miliary (many millet sized peritoneal implants) and non-miliary (few large exophytically growing peritoneal nodes), and an overall unfavorable outcome. HGSOC is thought to arise from fallopian tube secretory epithelial cells, via so called serous tubal intraepithelial carcinomas (STICs) but an ovarian origin was never ruled out for at least some cases. Comparative transcriptome analyses of isolated tumor cells from fresh HGSOC tissues and (immortalized) ovarian surface epithelial and fallopian tube secretory epithelial cell lines revealed a close relation between putative origin and tumor spread characteristic, i.e. miliary from tubes and non-miliary from ovaries. The latter were characterized by more mesenchymal cell characteristics, more adaptive tumor immune infiltration, and a favorable overall survival. Several molecular sub-classification systems (Crijns' overall survival signature, Yoshihara's subclasses, and a collagen-remodeling signature) seem to already indicate origin. Putative origin alone is a significant independent predictor for HGSOC outcome, validated in independent patient cohorts. Characteristics of both spread types could guide development of new targeted therapeutics, which are urgently needed.
authors.affiliation: Department of Obstetrics and Gynecology and Comprehensive Cancer Center (CCC), Medical University of Vienna, Vienna, Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Auer
authors.affiliation: Department of Obstetrics and Gynecology and Comprehensive Cancer Center (CCC), Medical University of Vienna, Vienna, Austria.
authors.forename: Anna
authors.initials: A
authors.lastname: Bachmayr-Heyda
authors.affiliation: Department of Obstetrics and Gynecology and Comprehensive Cancer Center (CCC), Medical University of Vienna, Vienna, Austria.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Aust
authors.affiliation: Signaling Networks Program, Division of Oncology, Department of Medicine I and Comprehensive Cancer Center (CCC), Medical University of Vienna, and Ludwig Boltzmann Cluster Oncology, Vienna, Austria.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Grunt
authors.affiliation: Section for Clinical Biometrics, Center for Medical Statistics, Informatics, and Intelligent Systems (CeMSIIS), Medical University of Vienna, Vienna, Austria; Department of Surgery, Medical University of Vienna, Vienna, Austria. Electronic address: dietmar.pils@univie.ac.at.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Pils
mesh_terms: D015331:Cohort Studies; D018284:Cystadenocarcinoma, Serous / Q000235:genetics* / Q000473:pathology; D005185:Fallopian Tube Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D055106:Genome-Wide Association Study; D006801:Humans; D060787:Neoplasm Grading; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D010053:Ovary; D010534:Peritoneal Neoplasms / Q000235:genetics* / Q000473:pathology; D059467:Transcriptome
keywords: Fallopian tube secretory epithelial cells; Miliary; Non-miliary; Ovarian surface epithelial cells; Tumor origin; Tumor spread