Protein and messenger ribonucleic acid (mRNA) for the type 1 insulin-like growth factor (IGF) receptor is decreased and IGF-II mRNA is increased in human prostate carcinoma compared to benign prostate epithelium.

Insulin-like growth factors (IGFs) and the type 1 IGF receptor (IGF-R) are involved in normal growth and development of the human prostate. Changes in levels of IGF-R and IGFs have been shown for several malignancies. Immunohistochemistry and in situ hybridization were performed to compare the expression of IGF-R and IGF-II in vivo in prostate tissue containing benign epithelium, high grade prostate intraepithelial neoplasia (PIN), and adenocarcinoma. Messenger ribonucleic acid (mRNA) hybridization signals and immunoreactivity for IGF-R were localized primarily to epithelial cells, with less signal in stroma. IGF-R mRNA was significantly decreased by 42% in PIN and 35% in cancer cells compared to that in benign epithelium (P < 0.0001). IGF-R immunostaining was significantly decreased by 32% in PIN and by 42% in malignant epithelium compared to that in benign epithelium (P < 0.004). IGF-II mRNA was also localized primarily to epithelial cells. IGF-II mRNA was significantly increased by 30% in adenocarcinoma compared to that in benign epithelium (P < 0.03). Immunoreactivity for IGF-II was localized to both stroma and epithelium. Protein levels for IGF-II were not significantly increased in cancer cells compared to those in benign epithelium. The decrease in the type 1 IGF receptor and increase in IGF-II mRNA may affect prostate cancer proliferation and differentiation.

Insulin-like growth factor-binding proteins (IGFBP)-4, -5, and -6 in the benign and malignant human prostate: IGFBP-5 messenger ribonucleic acid localization differs from IGFBP-5 protein localization.

Insulin-like growth factor (IGF)-binding proteins (IGFBPs) modulate the actions of IGF. We have previously reported that IGFBP-2 messenger ribonucleic acid (mRNA) and protein are increased, and IGFBP-3 protein decreased in malignant prostate epithelium compared to benign epithelium. In this study, we examined the other IGFBPs secreted by prostate cells in vitro, namely IGFBP-4, -5, and 6. Immunoreactivity and mRNA signals for IGFBP-4 and -6 were localized to epithelial cells, with less signal in stroma. IGFBP-4 immunostaining and hybridization signal were significantly increased in prostate adenocarcinoma compared to those in benign epithelium. Immunostaining for IGFBP-5 was localized to the epithelium and stroma. IGFBP-5 immunoreactivity was significantly increased in malignant compared to benign epithelium. IGFBP-5 mRNA signal was not localized to epithelial cells; rather, the signal was over stromal cells surrounding the acinar structures. These cells are thought to be fibroblasts. We show that IGFBP-4 mRNA and protein and IGFBP-5 protein are increased in malignant epithelium compared to benign epithelium, that IGFBP-6 is present in benign and malignant epithelium, and that there is differential localization of IGFBP-5 mRNA and protein in prostate tissue. IGFBP-5 that is made by fibroblasts appears to be sequestered by epithelial cells. IGFBP-5 may, therefore, be a factor in cellular interactions between stromal and epithelial cells that are of fundamental importance for normal prostatic development and function.

Immunohistochemical localization of insulin-like growth factor binding proteins 2 and 3 in prostate tissue: clinical correlations.

PURPOSE: The insulin-like growth factor system has recently been shown to have important mitogenic effects in the prostate. The system consists of 2 ligands: insulin-like growth factor types 1 and 2, which are potent mitogens for prostate cell growth, and 6 insulin-like growth factor binding proteins that modify the activity of these growth factors. Recently, changes in serum levels of insulin-like growth factor binding proteins 2 and 3 have been identified in prostate cancer patients but in vivo studies of these changes have not been previously reported. MATERIALS AND METHODS: We performed immunohistochemical staining for insulin-like growth factor binding proteins 2 and 3 in areas of benign disease, prostatic intraepithelial neoplasia, and cancer from specimens obtained from 24 patients who underwent prostatectomy to determine changes in the quantity of these proteins with progression from the benign through the premalignant and into the malignant states. Quantification of the differences noted in the amount of insulin-like growth factor binding proteins 2 and 3 found in each of the 3 tissue types was then correlated with serum and tissue prostate specific antigen levels, pathological stage and grade of the tumors. RESULTS: Our data indicate that as human prostate tissue progresses from the benign to the malignant state, insulin-like growth factor binding protein 2 immunoreactivity in the prostatic luminal epithelial cells increases and that of insulin-like growth factor binding protein 3 decreases. Quantification of the differences noted in binding proteins 2 and 3 among all 3 tissue types was statistically significant. However, no correlation was noted between the stage or grade of prostate carcinoma and insulin-like growth factor binding protein 2 or 3 immuno-staining intensity. Additionally, no significant correlation was found between serum or tissue levels of prostate specific antigen and insulin-like growth factor binding protein 2 or 3 immunoreactivity. CONCLUSIONS: Our data suggest that significant changes in the insulin-like growth factor system occur with malignant transformation in the prostate. It is hoped that this system may eventually result in a better serum or tissue (from prostate biopsy) marker of malignant transformation, and/or represent a target for early therapeutic intervention to alter the growth and development of prostate cancer.

Insulin-like growth factor-binding protein-2 and -3 expression in benign human prostate epithelium, prostate intraepithelial neoplasia, and adenocarcinoma of the prostate.

Insulin-like growth factor (IGF)-binding proteins (IGFBPs) modulate the activity of IGFs. In vitro human prostate epithelial cells secrete IGFBP-2 and -3. In vivo IGFBP-2 is increased, and IGFBP-3 is decreased in the serum of patients with prostate cancer. Immunohistochemistry and in situ hybridization were performed to compare the expression of IGFBP-2 and -3 in vivo in prostate tissue containing benign epithelium, high grade prostate intraepithelial neoplasia (PIN), and adenocarcinoma. Immunoreactivity and messenger ribonucleic acid (mRNA) hybridization signals for IGFBP-2 and -3 were localized to epithelial cells. IGFBP-2 immunostaining intensity was significantly increased in PIN regions compared to that in normal epithelium and was further increased in malignant cells. IGFBP-2 mRNA was also significantly increased in PIN and cancer cells. IGFBP-3 immunoreactivity was significantly increased in PIN regions compared to normal epithelium; however, IGFBP-3 protein was significantly decreased in malignant cells. IGFBP-3 mRNA remained virtually unchanged in benign epithelium, PIN, and adenocarcinoma cells. These results demonstrate that increased IGFBP-2 protein in PIN and malignant cells is probably due to increased mRNA expression. However, levels of IGFBP-3 protein may be due to pre- and/or posttranslational mechanisms, including proteolysis. The changes in IGFBP-2 and -3 protein levels in prostatic tissue are in agreement with serum changes reported in patients with prostate cancer.

Declining incidence of wound infection in cadaveric renal transplant recipient.

Over a five-year period 100 cadaveric renal transplants were performed. In 91 of these recipients, a prophylactic parenteral antibiotic (cefoperazone) was administered and closed wound drainage was used. Of these 91 patients, 33 received azathioprine/prednisone immunosuppression, whereas cyclosporine/prednisone with or without azathioprine was used in the remaining 58. The incidence of wound infections was significantly reduced from 12 per cent (4/33) in the azathioprine group to 1.7 per cent (1/58) in the cyclosporine group (p less than 0.01). When conventional immunosuppression (azathioprine/prednisone) is employed in renal transplantation, triple antibiotic prophylaxis that includes an aminoglycoside is most effective in preventing wound infections. A single non-nephrotoxic antibiotic, cefoperazone, offers similar protection in the cyclosporine/prednisone-treated renal transplant recipient.