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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
Author(s) -
Kramer G.,
Steiner G.E.,
Sokol P.,
Mallone R.,
Amann G.,
Marberger M.
Publication year - 2003
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1046/j.1464-410x.2003.04091.x
Subject(s) - atrophy , fetus , antigen , androgen , endocrinology , medicine , pathology , biology , pregnancy , immunology , hormone , genetics
As genes and their products are identified to play important roles in disease. Understanding what and how they are regulated has significant importance, as these gene products could then be blocked before they are expressed. NF‐κB represents an important transcription factor that drives the expression of specific gene product, ie proteins. The paper by Lessard et al. demonstrates the localization of this transcription factor in prostate cancer. Targeting this transcription factor could well represent an interesting therapeutic site to prevent the expression of proteins that may contribute to the development of the disease.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.