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Expression of human kallikrein 1-related peptidase 4 (KLK4) and MET phosphorylation in prostate cancer tissue: immunohistochemical analysis

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Abstract

Resistance to or relapse after androgen deprivation therapy (ADT) remains a significant problem in patients with prostate cancer. Several studies have hypothesized that the overexpression of MET and the activating signaling axis in prostate cancer cells are associated with castration-resistant prostate cancer (CRPC). On the other hand, the expression of human kallikrein 1-related peptidase (KLK) 4, which activates plasma HGF activator zymogen, in prostate cancer patients with bone metastasis or advanced stage has also been reported. In this study, we analyzed the expression and phosphorylation of MET along with KLK4 by immunohistochemistry in 62 formalin-fixed paraffin-embedded sections of prostate cancer collected by needle biopsy at our hospital between 2006 and 2011. As a result, the phosphorylation of MET was observed in 56 % (35 of 62 cases) and positively correlated with worsening PSA relapse rate in a group of ADT-treated patients (P = 0.0445), suggesting significant correlation with CRPC. Overexpression of KLK4 was observed in patients with high T stage (P = 0.0001) and high Gleason score (P = 0.0146), and the expression was correlated with the phosphorylation of MET (P = 0.0002). Pathologically, strong MET phosphorylation observed in specific architectures in prostate cancer, such as cribriform structures, ill-defined glands or solid patterns, suggested the significance of MET activation in promoting the architectural formation of prostate cancer. In addition, high positivity rate (80 %) of phospho-MET staining at high-grade prostatic intraepithelial neoplasia (HGPIN) may indicate the importance of the activating signaling axis in the carcinogenesis of prostate cancer.

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Acknowledgments

We would like to thank Ms. Yukari Kawagoe and Ms. Yasuko Tobayashi for their technical assistance with immunohistochemical staining. This study was supported in part by a grant for clinical research from Miyazaki University Hospital.

Conflict of interest

This study was supported in part by a grant for clinical research from Miyazaki University Hospital.

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Authors and Affiliations

  1. Department of Urology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan

    Shoichiro Mukai, Koji Yamasaki, Takahiro Nagai, Toyoharu Kamibeppu, Satoru Sugie, Kazutaka Kida, Chie Onizuka, Hiromasa Tsukino, Toshio Kamimura & Toshiyuki Kamoto

  2. Oncopathology and Regenerative Biology Section, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan

    Kenji Yorita & Hiroaki Kataoka

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  1. Shoichiro Mukai
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  2. Kenji Yorita
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Correspondence to Shoichiro Mukai.

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Mukai, S., Yorita, K., Yamasaki, K. et al. Expression of human kallikrein 1-related peptidase 4 (KLK4) and MET phosphorylation in prostate cancer tissue: immunohistochemical analysis. Human Cell 28, 133–142 (2015). https://doi.org/10.1007/s13577-015-0114-6

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  • DOI: https://doi.org/10.1007/s13577-015-0114-6

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