Expression of the apoptotic calcium channel P2X7 in the glandular epithelium.
In the current study, expression of the apoptotic calcium channel receptor P2X(7) 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 P2X(1 )and P2X(2) 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, P2X(1 )and P2X(2) 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 and E staining. In the current study, the apoptotic calcium channel receptor P2X(7) yielded similar results to that of P2X(1) and P2X(2). 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 or 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 P2X(7) labeling results. All patients who exhibited no P2X(7) labeling had a prostatic serum antigen (PSA) level of <2. Patients who exhibited stage-specific P2X(7) expression, and who later developed obvious prostate cancer as diagnosed by H and E stain, all had a PSA > 2. This finding suggests that increasing PSA may be an accurate indicator of cancer development.
Slater
Michael
M
Department of Anatomy and Histology, Institute for Biomedical Research, The University of Sydney, 2006 Sydney, NSW, Australia. Michaels@anatomy.usyd.edu.au
Danieletto
Suzanne
S
Barden
Julian A
JA
D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology*; D015415:Biomarkers; D001706:Biopsy; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D018048:Receptors, Purinergic P2 / Q000096:biosynthesis*; D058469:Receptors, Purinergic P2X; D058476:Receptors, Purinergic P2X2; D058486:Receptors, Purinergic P2X7
D015415:Biomarkers; C546401:P2RX2 protein, human; C546468:P2RX7 protein, human; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D058476:Receptors, Purinergic P2X2; D058486:Receptors, Purinergic P2X7; D017430:Prostate-Specific Antigen