Calcium-Sensing Receptor Tumor Expression and Lethal Prostate Cancer Progression.

Publication Type:

Journal Article

Source:

The Journal of clinical endocrinology and metabolism, Volume 101, Issue 6, p.2520-2527 (2016)

Abstract:

CONTEXT: Prostate cancer metastases preferentially target bone and the calcium sensing receptor (CaSR) may play a role in promoting this metastatic progression. OBJECTIVE: We evaluated the association of prostate tumor CaSR expression with lethal prostate cancer. DESIGN: A validated CaSR immunohistochemistry (IHC) assay was performed on tumor tissue microarrays (TMA). Vitamin D receptor expression and PTEN loss were previously assessed in a subset of cases by IHC. Cox proportional hazards models adjusting for age and BMI at diagnosis, Gleason grade, and pathologic TNM stage were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of CaSR expression with lethal prostate cancer. SETTING: The investigation was conducted in the Health Professionals Follow-up Study and Physicians' Health Study. PARTICIPANTS: We studied 1241 incident prostate cancer cases diagnosed between 1983 and 2009. MAIN OUTCOME: Participants were followed for cancer-specific mortality or development of metastatic disease. RESULTS: On average men were followed 13.6 years, during which there were 83 lethal events. High CaSR expression was associated with lethal prostate cancer independent of clinical and pathologic variables (HR=2.0; 95% CI=1.2-3.3). Additionally, there was evidence of effect modification by VDR expression; CaSR was associated with lethal progression among men with low tumor VDR expression (HR=3.2; 95% CI=1.4-7.3), but not in cases with high tumor VDR expression (HR=0.8; 95% CI=0.2-3.0). CONCLUSIONS: Tumor CaSR expression is associated with increased risk of lethal prostate cancer, particularly in tumors with low VDR expression. These results support further investigating the mechanism linking CaSR with metastases.