MODULATION OF CYTOKERATIN SUBTYPE, EGF RECEPTOR, AND ANDROGEN RECEPTOR EXPRESSION DURING PROGRESSION OF PROSTATE-CANCER

After initial regression in response to androgen deprivation, most pro state cancers develop resistance to endocrine therapy. Identification of cellular and molecular changes occurring during endocrine therapy-i nduced regression and subsequent hormone insensitivity may point to me chanisms underlying the transition to hormone-independent prostate can cer. A series of untreated (n = 24), repressed (n = 15), and endocrine therapy-resistant (n = 10) prostatic adenocarcinomas were analyzed us ing immunohistochemistry with regard to cytokeratin 5 and 18, androgen receptor (AR), and epidermal growth factor receptor (EGF-R) expressio n in tumor felts. Using semiquantitative reverse transcription-polymer ase chain reaction, the amount of AR mRNA also was determined. In regr essed and therapy-resistant prostate cancers, an increase in cytokerat in 5-positive tumor cells was noted when compared with untreated carci nomas. Similarly, the proportion of EGF-R-positive tumor cells increas ed in the treated cases, whereas the proportion of AR-positive tumor c ells dropped in regressed carcinomas and increased in hormone-refracto ry cancers. Ln the latter group, an eightfold higher level of AR mRNA was observed when compared with the other cases. Changes in the propor tion of cytokeratin 5 and EGF-R-positive tumor cells suggests chat dur ing androgen deprivation an enlarged subpopulation of tumor cells with combined features of basal and secretory phenotypes arises. The incre ased proportion of AR-positive tumor cells during the transition from the regression phase to the hormone escape phase points to an importan t role of AR overexpression in this process. Copyright (C) 1998 by W.B . Saunders Company.