QUANTITATIVE IMMUNOHISTOCHEMICAL ANALYSIS OF INSULIN-LIKE-GROWTH-FACTOR BINDING PROTEIN-3 IN HUMAN PROSTATIC ADENOCARCINOMA - A PROGNOSTIC STUDY

Purpose: We sought to characterize and quantitate the expression of IG FBP-3 in adenocarcinoma of the prostate and to test whether it correla ted with tumor differentiation determined by Gleason grade. We also in vestigated the potential of using IGFBP-3 as a prognostic indicator of clinically localized prostate cancer. Materials and Methods: Initiall y we evaluated the expression of IGFBP-3 in six normal and twenty neop lastic prostates using standard immunohistochemical techniques (study 1). We then obtained radical prostatectomy specimens from twenty-four patients with a preoperative diagnosis of clinically localized prostat e adenocarcinoma and five year follow up information, and nine normal prostates from organ donors or from patients undergoing cystoprostatec tomy (study 2). All specimens were immunostained with a polyclonal ant i-human IGFBP-3 antibody. A single pathologist reviewed all sections a nd assigned a Gleason grade to each cancer focus. Using computer-assis ted video image analysis, we quantified the intensity of IGFBP-3 immun ostaining of each cancer focus and of normal controls. Results: Normal prostatic epithelium showed intense cytoplasmic IGFBP-3 staining. The stromal compartment showed less intense staining, although there were occasional areas with strong immunoreactivity. The cellular distribut ion of IGFBP-3 staining in prostatic adenocarcinoma was comparable to normal tissue; however, the intensity of detectable staining in neopla stic epithelial cells was significantly decreased. Two foci of prostat ic intraepithelial neoplasia (PIN) demonstrated IGFBP-3 immunoreactivi ty decreased in comparison to normal epithelium, but greater than pros tatic adenocarcinoma. Histologically normal epithelium surrounding can cer foci also showed decreased immunostaining for IGFBP-3 compared wit h normal prostate. The marked decrease in immunostaining intensity of IGFBP-3 in prostate adenocarcinoma was not associated with Gleason gra de or with clinical outcome. Conclusion: Malignant transformation of p rostatic epithelium was associated with a significant decrease in the amount of immunoreactive IGFBP-3 (p < 0.0001); however, this parameter did not correlate with Gleason grade of the tumor or with patient out come. The decrease in immunostaining intensity of IGFBP-3 in all Gleas on grades and in PIN suggests that lower expression of IGFBP-3 is an e arly event in prostatic carcinogenesis. The finding that decreased IGF BP-3 immunostaining did not correlate with clinical outcome suggests t hat this parameter is not a therapy-guiding prognostic indicator for c linically localized prostate cancer.