title: Expression of human kallikrein 1-related peptidase 4 (KLK4) and MET phosphorylation in prostate cancer tissue: immunohistochemical analysis.
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.
authors: Department of Urology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan, syoichiro_mukai@med.miyazaki-u.ac.jp.
authors: Shoichiro
authors: S
authors: Mukai
authors: Kenji
authors: K
authors: Yorita
authors: Koji
authors: K
authors: Yamasaki
authors: Takahiro
authors: T
authors: Nagai
authors: Toyoharu
authors: T
authors: Kamibeppu
authors: Satoru
authors: S
authors: Sugie
authors: Kazutaka
authors: K
authors: Kida
authors: Chie
authors: C
authors: Onizuka
authors: Hiromasa
authors: H
authors: Tsukino
authors: Toshio
authors: T
authors: Kamimura
authors: Toshiyuki
authors: T
authors: Kamoto
authors: Hiroaki
authors: H
authors: Kataoka
mesh_terms: D000368:Aged; D063646:Carcinogenesis / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007610:Kallikreins / Q000235:genetics*; D008297:Male; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism*; D012189:Retrospective Studies; D015398:Signal Transduction / Q000235:genetics
chemical_list: C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D007610:Kallikreins; C120801:kallikrein 4