Stromal expression of Fer suppresses tumor progression in renal cell carcinoma and is a predictor of survival

  • Authors:
    • Kensuke Mitsunari
    • Yasuyoshi Miyata
    • Shin‑Ichi Watanabe
    • Akihiro Asai
    • Takuji Yasuda
    • Shigeru Kanda
    • Hideki Sakai
  • View Affiliations

  • Published online on: December 12, 2016     https://doi.org/10.3892/ol.2016.5481
  • Pages: 834-840
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Abstract

Fps/Fes related (Fer) is a non‑receptor tyrosine kinase that is expressed in fibroblasts, immune cells and endothelial cells. Fer serves an important pathological role in cell survival, angiogenesis and the immune system. However, the pathological role of Fer expression in the stromal cells surrounding renal cell carcinoma (RCC) has not been previously investigated. In the present study, immunohistochemical analysis of Fer was performed using the formalin‑fixed tissue samples of 152 patients with RCC. The proliferative and apoptotic indices were used to represent the percentage of proliferation marker protein Ki‑67‑ and cleaved caspase‑3‑positive cells, respectively. The microvessel density was defined as the number of cluster of differentiation (CD) 31‑positively stained vessels/mm2. In addition, CD57+ and CD68+ cells were counted using semi‑quantification of natural killer (NK) cells and macrophages. Fer expression in stromal cells was negatively associated with Fuhrman grade, pathological tumor stage and metastasis (P<0.001). Fer expression in stromal cells was negatively associated with CD68+ macrophage density, whereas it was positively associated with CD57+ NK cell density. Kaplan‑Meier estimators indicated that decreased stromal Fer expression was a predictive marker of decreased cause‑specific survival rate (P<0.001). Furthermore, low expression of Fer was identified as being an independent marker of decreased cause‑specific survival using multivariate analysis (hazard ratio, 7.4; 95% confidence interval, 1.7‑33.0; P<0.001). The results of the present study suggested that low Fer expression in stromal cells is associated with increased malignant aggressiveness and decreased survival in patients with RCC. CD57+ NK cell and CD68+ macrophage regulation in cancer‑stromal tissue is considered to affect RCC pathology.
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February-2017
Volume 13 Issue 2

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Mitsunari K, Miyata Y, Watanabe SI, Asai A, Yasuda T, Kanda S and Sakai H: Stromal expression of Fer suppresses tumor progression in renal cell carcinoma and is a predictor of survival. Oncol Lett 13: 834-840, 2017.
APA
Mitsunari, K., Miyata, Y., Watanabe, S., Asai, A., Yasuda, T., Kanda, S., & Sakai, H. (2017). Stromal expression of Fer suppresses tumor progression in renal cell carcinoma and is a predictor of survival. Oncology Letters, 13, 834-840. https://doi.org/10.3892/ol.2016.5481
MLA
Mitsunari, K., Miyata, Y., Watanabe, S., Asai, A., Yasuda, T., Kanda, S., Sakai, H."Stromal expression of Fer suppresses tumor progression in renal cell carcinoma and is a predictor of survival". Oncology Letters 13.2 (2017): 834-840.
Chicago
Mitsunari, K., Miyata, Y., Watanabe, S., Asai, A., Yasuda, T., Kanda, S., Sakai, H."Stromal expression of Fer suppresses tumor progression in renal cell carcinoma and is a predictor of survival". Oncology Letters 13, no. 2 (2017): 834-840. https://doi.org/10.3892/ol.2016.5481