LOSS OF LOW-AFFINITY NERVE GROWTH-FACTOR RECEPTOR DURING MALIGNANT TRANSFORMATION OF THE HUMAN PROSTATE

Background: The low-affinity nerve growth factor receptor (LNGFR) exhi bits an inverse association of epithelial expression with the degree o f differentiation of prostate adenocarcinoma tissue. However, the stag e at which loss of LNGFR expression is first manifested in the maligna nt prostate has not been determined. Methods: In order to characterize loss of LNGFR expression in the clinically localized malignant prosta te of untreated patients, the pattern of expression of the LNGFR was e xamined in nonmalignant tissues, consisting of normal and prostatic in traepithelial neoplastic tissues, and in malignant tissues that had be en graded by Gleason's scores and categorized into well, moderately, a nd poorly differentiated adenocarcinomas. In order to determine whethe r there was an inverse correlation between LNGFR expression and prosta te-specific antigen (PSA) secretion, preoperative concentrations of PS A in the serum were also analyzed in relation to the differentiative s tate of the adenocarcinomas. Results: Premalignant prostate tissues ex hibited expression of the LNGFR on all epithelia, whereas in malignant prostate tissues a proportion of epithelia exhibited loss of expressi on of the LNGFR. An increase in Gleason score of the adenocarcinoma ti ssue was associated with an increase in the proportion of epithelia th at exhibited loss of expression of the LNGFR. Moreover, the proportion of epithelia expressing the LNGFR was inversely correlated with an in crease in the concentration of serum PSA. The loss of LNGFR expression was first manifested in epithelia that occurred toward the center of adenocarcinoma tissue. Furthermore, extensive loss of expression of th e LNGFR of approximately 63% occurred in well-differentiated adenocarc inomas. Conclusions: These observations demonstrate that loss of LNGFR expression is first observed in well-differentiated malignant epithel ia. Hence, loss of the LNGFR may be indicative of the initial stages o f malignant transformation of prostate epithelia, as well as all subse quent stages of prostate adenocarcinomas. (C) 1997 Wiley-Liss, Inc.