Vasohibin-1 as a novel microenvironmental biomarker for patient risk reclassification in low-risk prostate cancer

// Hiroaki Kobayashi 1, * , Takeo Kosaka 1, * , Shuji Mikami 2 , Yasumasa Miyazaki 1 , Kazuhiro Matsumoto 1 , Eiji Kikuchi 1 , Akira Miyajima 1 , Kaori Kameyama 2 , Yasufumi Sato 3 and Mototsugu Oya 1 1 Department of Urology, Keio University School of Medicine, Tokyo, Japan 2 Division of Diagnostic Pathology, Keio University School of Medicine, Tokyo, Japan 3 Department of Vascular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan * These authors contributed equally to this work Correspondence to: Takeo Kosaka, email: takemduro@gmail.com Keywords: prostate cancer; vasohibin; prostatic biopsy; angiogenesis; immunohistochemistry Received: April 04, 2017 Accepted: November 26, 2017 Published: December 07, 2017 ABSTRACT Background: We previously reported high expression of vasohibin-1 (VASH1), which is specifically expressed in activated vascular endothelial cells, was a prognostic indicator of disease progression in prostate cancer. The aim of this study was to assess whether VASH1 expression at the area of normal prostatic tissue as well as that of intratumoral tissue could reflect the grade of malignancy of prostate cancer. Results: Pathological upgrade of Gleason Score ≥7 by radical prostatectomy was observed in 48 patients (upgraded group). The median VASH1 densities of the intratumoral and normal areas were 9.7 ± 9.5 and 13.3 ± 11.8, respectively, and the median MVDs were 58.6 ± 20.3 and 64.1 ± 23.5, respectively. We detected a strong positive correlation with each other for both VASH1 density ( ρ = 0.589, p < 0.001) and MVD ( ρ = 0.342, p < 0.001). VASH1 density was significantly higher in the upgreaded group than in the non-upgraded group regardless of prostatic location (intratumoral area: p < 0.001, normal area: p < 0.001). Conclusions: Even if the tumor volume was low in biopsy samples, VASH1 density reflected the grade of malignancy throughout the prostate. These results suggested that VASH1 expression could be a novel microenvironmental biomarker for patient risk reclassification in low-risk prostate cancer. Materials and Methods: Among the 1177 patients who underwent radical prostatectomy, 104 patients diagnosed with Gleason Score ≤6 and positive cores ≤3 were included. We immunohistochemically examined the microvessels positive for anti-CD34 as microvessel density (MVD), and those with activated endothelial cells as VASH1 density using prostatic biopsy samples, and evaluated the association between their expressions and clinicopathological findings.