Malignant transformation of human prostatic epithelium is associated with the loss of androgen receptor immunoreactivity in the surrounding stromal

The cellular pathways involved in the pathogenesis of hormone resistance re main unclear. Studies evaluating the role of changes in human androgen rece ptor (hAR) expression in the progression of prostatic tumors have been inco nclusive, Androgenic influence over prostatic growth is mediated via the re gulation of interactions between stromal and epithelial cells. We hypothesi zed that neoplastic transformation of the prostate would be associated with alterations in hAR expression in the adjacent stroma, Using immunohistoche mical techniques, we determined hAR positivity in the epithelium and adjace nt stroma of sections from 17 benign and 39 malignant prostatic glands. We found that whereas the expression of the receptor decreased in both cellula r compartments as the tissues dedifferentiated, the depletion was more pron ounced in the stromal nuclei (P < 0.0001). However, in sections from both u ntreated and hormone-resistant prostate cancer tissues, although heterogene ity of hAR expression in malignant epithelia was increased, there appeared to be a unique field effect around the cancerous prostate glands that resul ted in a decreased expression of the receptor in the adjacent benign glands and its total loss in the surrounding stroma, The loss of hAR in the strom a adjacent to malignant prostatic epithelium may play an important role in prostate cancer progression. Furthermore, the similarity of the lack of str omal hAR expression in newly diagnosed and hormone-resistant prostate cance r (P = 0.85) may be an indication that the mechanisms responsible for the a cquisition of hormone independence are established early in the malignant t ransformation process.