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Stromal Expression of Fibroblast Activation Protein Alpha (FAP) Predicts Platinum Resistance and Shorter Recurrence in patients with Epithelial Ovarian Cancer

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Cancer Microenvironment

Abstract

The microenvironment plays an important role in tumorigenesis. Fibroblast activation protein alpha (FAP) is overexpressed by fibroblasts present in the microenvironment of many tumors. High FAP expression is a negative prognostic factor in several malignancies, but this has not been investigated in epithelial ovarian cancer (EOC). The aim of this study is to define the value of FAP in EOC. Immunohistochemical staining using an anti-FAP antibody was performed on 338 EOC tissues. mRNA levels in cancer cell lines and FAP silencing using siRNA was also done. FAP immunoexpression by tumor stroma was a significant predictive factor for platinum resistance (p = 0.0154). In survival analysis of days to recurrence, FAP stoma+ was associated with shorter recurrence than those with FAP− stroma (p = 0.0247). In 21.8 % of tumors, FAP protein was expressed by the tumor epithelium, and FAP mRNA was more highly expressed in tumors (n = 489) than in normal tissues (n = 8) (p = 3.88 × 10−4). In vitro, addition of FAP to EOC cells induced a 10–12 % increase in cell viability both in the presence and absence of cisplatin. Conversely, siRNA silencing of FAP resulted in ~10 % reduction in EOC cell proliferation. We have shown that FAP expression in EOC is associated with poorer clinical outcomes. FAP may have novel cell-autonomous effects suggesting that targeting FAP could have pleiotropic anti-tumor effects, and anti-FAP therapy could be a highly effective novel treatment for EOC, especially in cisplatinum-resistant cases.

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Authors and Affiliations

  1. Department of Pathology, University of Southern California/Keck School of Medicine, Los Angeles, CA, USA

    Paulette Mhawech-Fauceglia, Maryam Sharifian & Grace Kim

  2. Department of Biostatistics, Roswell Park Cancer Institute, Buffalo, NY, USA

    Li Yan, Xing Ren & Song Liu

  3. Department of Preventive Medicine, University of Southern California/Keck School of Medicine, Los Angeles, CA, USA

    Simon A. Gayther & Kate Lawrenson

  4. Department of Gynecologic Oncology at Oregon Health & Science University and the Knight Cancer Institute, Portland, Oregon

    Tanja Pejovic

  5. Division of Gyneoclogic Pathology, LAC+USC Medical Center, 1100 N. State St, Outpatient Tower, Rm. 7A116, Los Angeles, CA, 90033, USA

    Paulette Mhawech-Fauceglia

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  1. Paulette Mhawech-Fauceglia
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  2. Li Yan
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  3. Maryam Sharifian
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  4. Xing Ren
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Correspondence to Paulette Mhawech-Fauceglia.

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Mhawech-Fauceglia, P., Yan, L., Sharifian, M. et al. Stromal Expression of Fibroblast Activation Protein Alpha (FAP) Predicts Platinum Resistance and Shorter Recurrence in patients with Epithelial Ovarian Cancer. Cancer Microenvironment 8, 23–31 (2015). https://doi.org/10.1007/s12307-014-0153-7

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  • DOI: https://doi.org/10.1007/s12307-014-0153-7

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