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.

Determining the risk that a particular area of hyperplastic breast tissue will progress to cancer is difficult and is currently expressed only as a general risk factor within the population. Using an antibody against the apoptotic purinergic receptor P2X7, we examined 40 cases each of the following histological categories: normal, moderate, florid and atypical hyperplasia, lobular carcinoma in situ, ductal carcinoma in situ, invasive lobular and invasive ductal carcinoma. These were previously diagnosed by H&E and supplied by clinical laboratories as tissue sections. Normal and mildly hyperplastic epithelium was devoid of the cytolytic P2X7 receptors whereas all epithelial cells in all cases of in situ or invasive lobular or ductal carcinoma labelled intensely. The lobular and ductal in situ cases labelled intracellularly while the invasive epithelial cancer cells showed intense cell surface label indicating an attempt was being made to induce apoptosis. All these receptors however are non-functional and thus unable to induce apoptosis. Approximately 10% of all hyperplastic lobules examined in the biopsied tissue, regardless of H&E classification, labelled for P2X7, which is suggestive of early metabolic cancerous change. The acini within lobules were either completely labelled with P2X7 or were completely devoid of the receptor. A potential advantage of this method lies in identifying early cancerous change in hyperplastic lobules and in establishing the true extent of cancerous spread in infiltrating lesions, thus facilitating the task of reporting clear surgical margins.

SummaryBackground Expression of P2X 7 , an ATP-gated calcium channel, increases cancer cell proliferation and invasiveness. A variant of P2X 7 (termed nfP2X 7 ), in which a normally hidden epitope (E200) is exposed for antibody binding, is observed in a variety of different cancers. Objectives To investigate the safety, tolerability and pharmacokinetics and assess indicative efficacy of a novel antibody ointment as a therapeutic for basal cell carcinoma (BCC). Methods An open-label, phase I clinical trial was undertaken at three dermatology clinics to evaluate the safety and tolerability of topical administration of an ointment containing 10% sheep polyclonal anti-nfP2X 7 antibodies (BIL010t) to primary BCC lesions twice daily for 28 days. Twenty-one patients with primary BCC lesions at least 0Á5 cm 2 in area and less than 2Á0 cm in diameter were enrolled. The primary end points were safety, tolerability and pharmacokinetics. Change in lesion size after treatment was determined and histology was performed on pretreatment and end-of-treatment (EOT) biopsies. Results Compliance was very high, with treatment being well tolerated. The most common adverse events were treatment site erythema, pruritus, dryness and pain. There was no evidence of systemic penetration of the sheep antibody. Lesions were measured prior to and after 28 days of treatment, with 65% of patients showing a reduction in lesion area, 20% showing no change and 15% showing an increase. Histopathology of post-treatment excision of lesion sites showed eight patients with stable disease, nine with partial response and three with complete response. Conclusions Antibodies against nfP2X 7 (BIL010t) provide a novel, safe and welltolerated treatment for BCC.

No abstract