title: Peritoneal tumor spread in serous ovarian cancer-epithelial mesenchymal status and outcome.
abstract: In this study we aimed to analyze the biological mechanisms underlying apparently different modes of peritoneal tumor spread in serous ovarian cancer: miliary (widespread, millet-like lesions) versus non-miliary (bigger, exophytically growing implants). Tumor tissues and ascites from 23 chemotherapy naive patients were analyzed by RNA-sequencing and flow cytometry. On the basis of differential gene expression between miliary and non-miliary, gene signatures were developed. A calculated tumor spread factor revealed a significant independent negative impact of miliary spread on overall survival (HR 3.77; CI95 1.14-12.39; p = 0.029) in an independent cohort of 165 serous ovarian cancer patients. Comparing previously published epithelial-mesenchymal transition (EMT) gene signatures, non-miliary spread correlated significantly with a reduced epithelial status. We conclude that serous ovarian cancer is a heterogeneous disease with distinct modes of peritoneal tumor spread, differing not only in clinical appearance, but also in molecular characteristics and outcome. EMT, peritoneal inflammation status, and therapeutic options are discussed.
  
  
  CONCLUSIONS
  More than half of serous epithelial ovarian cancer patients present with a newly described type of intraperitoneal tumor spread, associated with differences in the inflammation status, activated oncogenic pathways, lack of EMT, and thus reduced overall survival. Both, the diminished immune reaction and the enhanced epithelial and malignant characteristics of the tumor cells open new avenues for therapeutic options and strategies, like Catumaxomab, already in clinical use.
authors.affiliation: Department of Obstetrics and Gynecology, Comprehensive Cancer Center (CCC), Medical University of Vienna and Ludwig Boltzmann Cluster Translational Oncology, Vienna, Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Auer
authors.affiliation: Department of Obstetrics and Gynecology, Comprehensive Cancer Center (CCC), Medical University of Vienna and Ludwig Boltzmann Cluster Translational Oncology, Vienna, Austria.
authors.forename: Anna
authors.initials: A
authors.lastname: Bachmayr-Heyda
authors.affiliation: Department of Obstetrics and Gynecology, Comprehensive Cancer Center (CCC), Medical University of Vienna and Ludwig Boltzmann Cluster Translational Oncology, Vienna, Austria.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Aust
authors.affiliation: Department of Obstetrics and Gynecology, Comprehensive Cancer Center (CCC), Medical University of Vienna and Ludwig Boltzmann Cluster Translational Oncology, Vienna, Austria.
authors.forename: Nyamdelger
authors.initials: N
authors.lastname: Sukhbaatar
authors.affiliation: Department of Obstetrics and Gynecology, Comprehensive Cancer Center (CCC), Medical University of Vienna and Ludwig Boltzmann Cluster Translational Oncology, Vienna, Austria.
authors.forename: Agnes Teresa
authors.initials: AT
authors.lastname: Reiner
authors.affiliation: Department of Obstetrics and Gynecology, Comprehensive Cancer Center (CCC), Medical University of Vienna and Ludwig Boltzmann Cluster Translational Oncology, Vienna, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Grimm
authors.affiliation: Department of Pathology, Medical University of Vienna, Vienna, Austria.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Horvat
authors.affiliation: Department of Obstetrics and Gynecology, Comprehensive Cancer Center (CCC), Medical University of Vienna and Ludwig Boltzmann Cluster Translational Oncology, Vienna, Austria.
authors.forename: Robert
authors.initials: R
authors.lastname: Zeillinger
authors.affiliation: Department of Obstetrics and Gynecology, Comprehensive Cancer Center (CCC), Medical University of Vienna and Ludwig Boltzmann Cluster Translational Oncology, Vienna, Austria.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Pils
mesh_terms: D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000401:mortality / Q000556:secondary*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D010534:Peritoneal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000556:secondary*; D016016:Proportional Hazards Models; D059467:Transcriptome
keywords: RNA-sequencing; epithelial ovarian cancer; flow cytometric analysis; next generation sequencing; peritoneal tumor spread