Early prostate cancer detected using expression of non‐functional cytolytic P2X₇ receptors

Abstract

AIMS: To detect early prostate cancer reliably by monitoring the expression of non-functional P2X(7) cytolytic purinergic receptors. METHODS AND RESULTS: P2X(7) receptors were absent from normal prostate epithelium obtained from post mortem tissue and tissue from cases of transurethral resection collected from young men (n = 23) who were confirmed to be free of cancer at later procedures 5-10 years after collection of the original samples. However, P2X(7) was present in every case of 116 confirmed prostate cancers regardless of Gleason grade or patient age. P2X(7) was present in apparently normal epithelial cells in acini well outside the tumour margins, but appeared in a distinct stage-specific manner commencing with the nucleus, progressing to the cytoplasm and collecting finally on the apical membrane of the epithelial cells in morphologically distinct cancer. The pattern of P2X(7) receptor localization in the epithelial cells was recorded in earlier biopsies obtained from the same patient cohort. One hundred and fourteen of 116 prostates stained positively for P2X(7) at the earliest biopsy, though generally with a less advanced pattern of distribution. CONCLUSIONS: The appearance of P2X(7) receptors in normal prostate tissue adjacent to prostate tumours makes direct tumour biopsy less critical for positive cancer diagnosis and enables cancer progression to be monitored.