Abstract

The stem cell factor (SCF) receptor CD117 (c-kit), is widely used for identification of hematopoietic stem cells and cancer stem cells. Moreover, CD117 expression in carcinoma cells indicates a poor prognosis in a variety of cancers. However the potential expression in tumor microenvironment and the biological and clinical impact are currently not reported. The expression of CD117 was immunohistochemically evaluated in a serial of 242 epithelial ovarian cancer (EOC) cases. Thirty-eight out of 242 cases were CD117 positive in fibroblast-like stromal cells and 22 cases were positive in EOC cells. Four cases were both positive in fibroblast-like stromal cells and EOC cells for CD117. CD117 expression in fibroblast-like stromal cells in ovarian carcinoma was closely linked to advanced FIGO stage, poor differentiation grade and histological subtype (p<0.05), and it was significantly associated with poor overall survival (OS) and progression free survival (PFS) (Kaplan-Meier analysis; p<0.05, log-rank test). CD117 expression in ovarian carcinoma cells was not associated with these clinicopathological variables. The CD117 positive fibroblast-like stromal cells were all positive for mesenchymal stem/stromal cell (MSC) marker CD73 but negative for fibroblast markers fibroblast activation protein (FAP) and α smooth muscle actin (α-SMA), indicating that the CD117+/CD73+ fibroblast-like stromal cells are a subtype of mesenchymal stem cells in tumor stroma, although further characterization of these cells are needed. It is concluded herewith that the presence of CD117+/CD73+ fibroblast-like stromal cells in ovarian carcinoma is an unfavorable clinical outcome indication.

Highlights

  • Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy worldwide [1,2]

  • To better understand CD117 expression in ovarian carcinoma cells and stromal cells and the clinicopathological associations, we investigated CD117 expression in 242 formalin-fixed paraffin

  • CD117 positive fibroblast-like stromal cells were further identified by mesenchymal stem/stromal cell (MSC) marker CD73 (NT5E) and cancer associated fibroblast (CAF) markers fibroblast activation protein (FAP) and a-smooth muscle actin (a-SMA)

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Summary

Introduction

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy worldwide [1,2]. Most women with EOC are diagnosed at an advanced stage. The 5-year survival is less than 30% for the women diagnosed at advanced stage [2]. Cancer stem cells (CSCs) represent a subpopulation of tumor cells responsible for tumor initiation, progression, invasion, metastasis and relapse, and are capable of cell renewal. Tumor microenvironment is the cellular environment in which tumor cells exist, including blood vessels, immune cells, fibroblasts, macrophages, extracellular matrix (ECM) and other molecules, etc. The stromal cells interact with each other in a complex net by secreting distinct, abnormal molecules into ECM and contribute to tumor growth and invasiveness [3,4,5,6,7]. Tumor stromal cells from different tissue have different gene expression profiles and contribute to tumor heterogeneity [8]. It is necessary to develop new tumorpreventive methods to target tumor microenvironment and to interfere carcinogenesis [9]

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