TRPM4 protein expression in prostate cancer: a novel tissue biomarker associated with risk of biochemical recurrence following radical prostatectomy

TY - JOUR

T1 - TRPM4 protein expression in prostate cancer

T2 - a novel tissue biomarker associated with risk of biochemical recurrence following radical prostatectomy

AU - Berg, Kasper Drimer

AU - Soldini, Davide

AU - Jung, Maria

AU - Dietrich, Dimo

AU - Stephan, Carsten

AU - Jung, Klaus

AU - Dietel, Manfred

AU - Vainer, Ben

AU - Kristiansen, Glen

PY - 2016/3/1

Y1 - 2016/3/1

N2 - Background Transient receptor potential cation channel, subfamily M, member 4 (TRPM4) messenger RNA (mRNA) has been shown to be upregulated in prostate cancer (PCa) and might be a new promising tissue biomarker. We evaluated TRPM4 protein expression and correlated the expression level with biochemical recurrence (BR) following radical prostatectomy (RP). Material and methods The study included 614 patients who had undergone RP. TRPM4 immunohistochemical staining was performed on samples of benign tissue, tissue containing PIN glands and PCa tissue using a commercially available polyclonal antibody. Staining intensity was recorded by two independent observers using a four-tired semi-quantitative grading system (0, 1+, 2+, 3+) converted into H-scores. Interobserver agreement was calculated by linear weighted kappa statistics. The association between staining intensity and BR was analysed using the Kaplan-Meier estimator and uni- and multiple Cox proportional hazard regression models. Results Significantly higher staining intensity was found in PCa glands compared to benign glands (p<0.001). The concordance rate in TRPM4 staining intensities for benign, PIN and PCa tissue ranged from 86.0 to 91.5%, corresponding to linear weighted kappa values of 0.566–0.789. After adjusting for patient and tumour characteristics, patients with a higher staining intensity in PCa glands compared to matched benign glands and an H-score equal to or above the median had an increased risk of BR (HR 1.79–2.62; p=0.01–0.03 for the two observers) when compared to patients with a lower staining intensity. Conclusions TRPM4 protein expression is widely expressed in benign and cancerous prostate tissue, with highest staining intensities found in PCa. Overexpression of TRPM4 in PCa (combination of high staining intensity and a high H-score) is associated with increased risk of BR after RP.

AB - Background Transient receptor potential cation channel, subfamily M, member 4 (TRPM4) messenger RNA (mRNA) has been shown to be upregulated in prostate cancer (PCa) and might be a new promising tissue biomarker. We evaluated TRPM4 protein expression and correlated the expression level with biochemical recurrence (BR) following radical prostatectomy (RP). Material and methods The study included 614 patients who had undergone RP. TRPM4 immunohistochemical staining was performed on samples of benign tissue, tissue containing PIN glands and PCa tissue using a commercially available polyclonal antibody. Staining intensity was recorded by two independent observers using a four-tired semi-quantitative grading system (0, 1+, 2+, 3+) converted into H-scores. Interobserver agreement was calculated by linear weighted kappa statistics. The association between staining intensity and BR was analysed using the Kaplan-Meier estimator and uni- and multiple Cox proportional hazard regression models. Results Significantly higher staining intensity was found in PCa glands compared to benign glands (p<0.001). The concordance rate in TRPM4 staining intensities for benign, PIN and PCa tissue ranged from 86.0 to 91.5%, corresponding to linear weighted kappa values of 0.566–0.789. After adjusting for patient and tumour characteristics, patients with a higher staining intensity in PCa glands compared to matched benign glands and an H-score equal to or above the median had an increased risk of BR (HR 1.79–2.62; p=0.01–0.03 for the two observers) when compared to patients with a lower staining intensity. Conclusions TRPM4 protein expression is widely expressed in benign and cancerous prostate tissue, with highest staining intensities found in PCa. Overexpression of TRPM4 in PCa (combination of high staining intensity and a high H-score) is associated with increased risk of BR after RP.

U2 - 10.1007/s00428-015-1880-y

DO - 10.1007/s00428-015-1880-y

M3 - Journal article

C2 - 26590985

SN - 0945-6317

VL - 468

SP - 345

EP - 355

JO - Virchows Archiv

JF - Virchows Archiv

IS - 3

ER -