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

Abstract

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.

• Authors: Kasper Drimer Berg, Davide Soldini, Maria Jung, Dimo Dietrich, Carsten Stephan, Klaus Jung, Manfred Dietel, Ben Vainer, Glen Kristiansen
• Journal: Virchows Archiv : an international journal of pathology (Virchows Arch) Vol. 468 Issue 3 Pg. 345-55 (Mar 2016) ISSN: 1432-2307 [Electronic] Germany
• PMID: 26590985 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• TRPM Cation Channels
• TRPM4 protein, human

Topics

• Biomarkers, Tumor (metabolism)
• Disease-Free Survival
• Humans
• Immunohistochemistry (methods)
• Male
• Prostatectomy (methods)
• Prostatic Neoplasms (metabolism, pathology)
• Recurrence
• Risk
• TRPM Cation Channels (metabolism)