Ovarian low and high grade serous carcinomas: hidden divergent features in the tumor microenvironment
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Alessandra Ciucci1,*, Gian Franco Zannoni2,*, Marianna Buttarelli1, Enrica Martinelli1, Floriana Mascilini3, Marco Petrillo3, Gabriella Ferrandina3,4, Giovanni Scambia3, Daniela Gallo1
1Unit of Translational Medicine for Women and Children Health, Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy
2Department of Pathology, Catholic University of the Sacred Heart, Rome, Italy
3Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy
4Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy
*These authors contributed equally to this work
Daniela Gallo, email: [email protected]
Keywords: ovary, tumor-associated macrophages, TAM, M1, M2
Received: May 26, 2016 Accepted: July 13, 2016 Published: July 23, 2016
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.
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