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Loss of CD38 correlates with simultaneous up-regulation of human leukocyte antigen-DR in benign prostatic glands, but not in fetal or androgen-ablated glands, and is strongly related to gland atrophy.
OBJECTIVE: To determine whether CD38 loss in benign and malignant prostatic disease is related to human leukocyte antigen (HLA)-DR up-regulation, by assessing the histopathology of the prostate and the effect of androgen deprivation.
MATERIALS AND METHODS: Serial sections of frozen fetal (eight), infant (six), normal adult (10), benign hyperplastic (BPH, 24), and primary (10) and hormone-treated (11) carcinomatous human prostatic tissues were analysed by immunohistology for anti-CD38 and HLA-DR antigens.
RESULTS: In BPH samples there was a significant correlation between CD38 loss (mean 21% of acini) and HLA-DR up-regulation (mean 20%; P < 0.001). Moreover, 76% of all CD38-negative acini in BPH had HLA-DR up-regulation in the same prostate epithelial cells, predominantly in atrophic and cystic glands, and in cells with retained secretions (74%). In contrast to the uniform expression in normal adult prostate, CD38 was negative or partly expressed in fetal acini (mean 19%) and almost completely negative in acini of the early infant period (mean 0.7%). In contrast to BPH, cancer cells did not selectively up-regulate HLA-DR when CD38 was lost. In patients with cancer treated by androgen deprivation, cancer cells were CD38-negative.
CONCLUSIONS: The absence of CD38 and presence of HLA-DR expression in prostatic epithelium is consistent in BPH and tissue surrounding tumour, and strongly related to gland atrophy. This is particularly interesting as HLA-DR triggering can induce apoptosis of cells, whereas CD38 prevents it. A permissive role for androgens to maintain full CD38 expression in epithelial cells is suggested.
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