title: Ovarian low and high grade serous carcinomas: hidden divergent features in the tumor microenvironment.
abstract: Only recently low-grade serous carcinoma (LGSOC) of the ovary has been recognized as a disease entity distinct from the more common high-grade serous carcinoma (HGSOC), with significant differences in pathogenesis and clinical and pathologic features. The present study aimed at evaluating whether the different natural histories and patterns of response to therapy demonstrated for LGSOC and HGSOC, along with a diverse genomic landscape, may also reside in the supporting tumor stroma, specifically in the state of differentiation and activation of tumor associated macrophages (TAMs). TAMs play complex roles in tumorigenesis since they are believed to possess both tumor rejecting (M1 macrophages) and tumor promoting (M2 macrophages) activities. Here we showed that, when compared to HGSOC (n = 55), LGSOC patients (n = 25) exhibited lower density of tumor-infiltrating CD68+ macrophage, along with an attenuated M2-skewed (CD163+) phenotype. Accordingly, assessment of intratumoral vascularization and of matrix metalloproteinase 9 expression (a key protein involved in tumor invasion and metastasis) revealed lower expression in LGSOC compared to HGSOC patients, in line with emerging evidence supporting a role for TAMs in all aspects of tumor initiation, growth, and development. In conclusion, results from the present study demonstrate that microenvironmental factors contribute greatly to determine clinical and pathological features that differentiate low and high grade serous ovarian carcinomas. This understanding may increase possibilities and opportunities to improve disease control and design new therapeutic strategies.
authors.affiliation: Unit of Translational Medicine for Women and Children Health, Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ciucci
authors.affiliation: Department of Pathology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Gian Franco
authors.initials: GF
authors.lastname: Zannoni
authors.affiliation: Unit of Translational Medicine for Women and Children Health, Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Buttarelli
authors.affiliation: Unit of Translational Medicine for Women and Children Health, Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Martinelli
authors.affiliation: Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Floriana
authors.initials: F
authors.lastname: Mascilini
authors.affiliation: Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Petrillo
authors.affiliation: Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.|Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Ferrandina
authors.affiliation: Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scambia
authors.affiliation: Unit of Translational Medicine for Women and Children Health, Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Gallo
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D018284:Cystadenocarcinoma, Serous / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008264:Macrophages / Q000145:classification / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D060787:Neoplasm Grading; D009389:Neovascularization, Pathologic / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D011956:Receptors, Cell Surface / Q000378:metabolism; D012189:Retrospective Studies; D059016:Tumor Microenvironment; D000098902:CD163 Antigen; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D020780:Matrix Metalloproteinase 9; D011956:Receptors, Cell Surface; D000098902:CD163 Antigen; C067980:CD68 antigen, human; D000097382:CD68 Molecule
keywords: M1; M2; TAM; ovary; tumor-associated macrophages