Expression of the apoptotic calcium channel P2X₇ in the glandular epithelium

Abstract

In the current study, expression of the apoptotic calcium channel receptor P2X₇ and prostate-specific antigen (PSA) levels were studied in biopsy cores from 174 patients as well as 20 radical prostatectomy cases. In clinical biopsies, we have previously demonstrated that P2X₁ and P2X₂ calcium channel receptors are absent from normal prostate epithelium that does not progress to prostate cancer within 5 years. In cases that did progress to prostate cancer however, P2X₁ and P2X₂ labeling was observed in a stage-specific manner first in the nucleus, then the cytoplasm and finally on the apical epithelium, as prostate cancer developed. These markers were present up to 5 years before cancer was detectable by the usual morphological criteria (Gleason grading) as determined by H&E staining. In the current study, the apoptotic calcium channel receptor P2X₇ yielded similar results to that of P2X₁ and P2X₂. Using radical prostatectomy tissue sections as well as biopsies, these changes in calcium channel metabolism were noted throughout the prostate, indicating a field effect. This finding suggests that the presence of a prostate tumor could be detected without the need for direct sampling of tumor tissue, leading to detection of false negative cases missed by H&E stain. The reliability of PSA levels as a prognostic indicator has been questioned in recent years. In the current study, PSA levels were correlated with the P2X₇ labeling results. All patients who exhibited no P2X₇ labeling had a prostatic serum antigen (PSA) level of <2. Patients who exhibited stage-specific P2X₇ expression, and who later developed obvious prostate cancer as diagnosed by H&E stain, all had a PSA > 2. This finding suggests that increasing PSA may be an accurate indicator of cancer development.