Immunohistochemical comparative analysis of transforming growth factor alpha, epidermal growth factor, and epidermal growth factor receptor in normal, hyperplastic and neoplastic human prostates.
Immunoreaction to TGF-alpha was limited to the basal epithelial cells of focal areas in the normal prostates. In benign prostatic hyperplasia (BPH) the immunostained areas were more widespread and immunolabelling was observed in both basal and columnar (secretory) cells of the epithelium. Some cells in the connective tissue stroma were also stained. In prostatic adenocarcinoma, epithelial immunostaining was even more extensive and intense than in BPH, and some stromal cells were also stained. Epidermal growth factor (EGF) immunostaining was only present in some basal cells in normal prostates. In BPH, this immunoreaction was strong in the basal cells and even stronger in the secretory cells. In prostatic cancer, the intensity of epithelial cell immunoreactivity was intermediate between that of normal prostates and that of BPH specimens. EGF-receptor immunostaining was focal and located in the basal cells in normal prostates. In BPH, labelling was also localized in basal cells but extended to wider areas. Some stromal cells appeared weakly labelled. In the prostatic carcinoma, both basal and columnar cells appeared stained and the number of immunolabelled stromal cells was higher than in BPH. The results presented suggest that, in normal conditions, EGF and TGF-alpha act as autocrine growth factors for the basal cells of the prostatic epithelium. In BPH this action is maintained and, in addition, the columnar cells start to secrete both factors which are bound by the basal cell receptors, giving rise to a paracrine regulation which probably overstimulates basal cell proliferation. In prostatic carcinoma, besides these regulatory mechanisms, the acquisition of EGF-receptors by the secretory cells develops an autocrine regulation which might induce their proliferation.
De Miguel
P
P
Department of Cell Biology and Genetics, University of Alcalá, Madrid, Alcalá de Henares, E-28871, Spain.
Royuela
Bethencourt
R
R
Ruiz
A
A
Fraile
B
B
Paniagua
R
R
D000230:Adenocarcinoma / Q000737:chemistry*; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000918:Antibody Specificity; D003238:Connective Tissue / Q000737:chemistry; D004815:Epidermal Growth Factor / Q000032:analysis*; D004847:Epithelial Cells / Q000737:chemistry; D066246:ErbB Receptors / Q000032:analysis*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D009928:Organ Specificity; D011467:Prostate / Q000737:chemistry*; D011470:Prostatic Hyperplasia / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000737:chemistry*; D011817:Rabbits; D017154:Stromal Cells / Q000737:chemistry; D016211:Transforming Growth Factor alpha / Q000032:analysis*
D009363:Neoplasm Proteins; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D066246:ErbB Receptors