Detection of preneoplasia in histologically normal prostate biopsies

P2X immunolabeling of prostate detected preneoplastic changes in apparently normal tissue. Labeling occurred in two well-defined stages before the dia gnostic histological markers of cancer were visible. As cancer progressed, the location of P2X expression changed from confinement within individual n uclei in the acini (stage 1) to a cytoplasmic punctate label in the acinal epithelium, with an associated removal of nuclear stain (stage 2). Finally, in advanced cases, where clear morphological evidence of cancer was appare nt, the P2X label condensed exclusively on the apical epithelium (stage 3). BPH/normal tissue was entirely devoid of P2X label. Biopsy samples (77) we re tested in three categories. One group (35) were diagnosed as normal beni gn prostatic hyperplasia (BPH) on the basis of haematoxylin and eosin (H&E) stain, although underlying disease was suspected. Of these, 14 (40%) were clearly normal and appeared entirely devoid of label, 13 (37%) exhibited th e first stage of P2X receptor labeling and the remaining eight (23%) exhibi ted second stage labeling. The accompanying H&E-stained sections of all the se cases had a normal appearance. Low grade cancer biopsy samples with Glea son scores G4-7 (25) all revealed widespread second stage receptor labeling in areas of both normal and cancerous morphology, while 17 high grade canc er biopsy samples (Gleason G8-10) all showed third stage labeling along wit h some residual second stage labeling. The features of each P2X labeling st age occupied the entire histological area affected, offering more opportuni ty to diagnose the tissue than was supplied by the more-localised diagnosti c features identified by H&E-stain. Besides detecting cases of preneoplasia in biopsies with a normal H&E appearance, this technique was also able to rule out the presence of neoplasia in purely hyperplasic prostates by the a bsence of any P2X labeling.