LOSS OF UTEROGLOBIN EXPRESSION IN PROSTATE-CANCER - RELATIONSHIP TO ADVANCING GRADE

We have shown previously that the secretory protein uteroglobin (UG) i s highly expressed in normal human prostate tissue but this expression is either lost or altered in human prostate cancer cell lines. Treatm ent of these cell lines with recombinant human UG inhibits their abili ty to invade human reconstituted basement membrane by up to 90%, imply ing that the loss of normal UG expression may be related to the invasi ve potential of prostate cancer. Because invasion represents a critica l step in metastasis, the expression patterns of UG could provide a un ique and relevant indicator of cancer progression. In this study, we p resent the immunohistochemical analyses of fresh frozen prostate tissu es from surgical specimens taken from 50 patients. Eight slides per pa tient were analyzed for UG staining. Slides from 26 patients showed ev idence of prostate cancer, whereas slides from the remaining 24 patien ts showed only benign glands. The results demonstrate UG immunoreactiv ity in normal prostate, benign prostatic hyperplasia, and prostatic at rophy; low but clearly positive expression in prostatic intraepithelia l neoplasia; positive expression in cancerous glands of Gleason's patt ern less than or equal to 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 pros tate cancer cells within the lymph node lacked UG expression. These fi ndings suggest that the loss of UG expression may be an indicator of p rostate cancer progression and possibly a component of the molecular n atural history of prostate cancer, which may have prognostic value.