Loss of uteroglobin expression in prostate cancer: relationship to advancing grade.

We have shown previously that the secretory protein uteroglobin (UG) is highly expressed in normal human prostate tissue but this expression is either lost or altered in human prostate cancer cell lines. Treatment of these cell lines with recombinant human UG inhibits their ability to invade human reconstituted basement membrane by up to 90%, implying that the loss of normal UG expression may be related to the invasive potential of prostate cancer. Because invasion represents a critical step in metastasis, the expression patterns of UG could provide a unique and relevant indicator of cancer progression. In this study, we present the immunohistochemical analyses of fresh frozen prostate tissues from surgical specimens taken from 50 patients. Eight slides per patient were analyzed for UG staining. Slides from 26 patients showed evidence of prostate cancer, whereas slides from the remaining 24 patients showed only benign glands. The results demonstrate UG immunoreactivity in normal prostate, benign prostatic hyperplasia, and prostatic atrophy; low but clearly positive expression in prostatic intraepithelial neoplasia; positive expression in cancerous glands of Gleason's pattern </=2; and complete loss of UG immunoreactivity in cancerous glands of Gleason's pattern 3 or greater. In addition, in the one case of metastatic prostate cancer that we examined, the prostate cancer cells within the lymph node lacked UG expression. These findings suggest that the loss of UG expression may be an indicator of prostate cancer progression and possibly a component of the molecular natural history of prostate cancer, which may have prognostic value.