Modulation of cytokeratin subtype, EGF receptor, and androgen receptor expression during progression of prostate cancer.
After initial regression in response to androgen deprivation, most prostate cancers develop resistance to endocrine therapy. Identification of cellular and molecular changes occurring during endocrine therapy-induced regression and subsequent hormone insensitivity may point to mechanisms underlying the transition to hormone-independent prostate cancer. A series of untreated (n = 24), regressed (n = 15), and endocrine therapy-resistant (n = 10) prostatic adenocarcinomas were analyzed using immunohistochemistry with regard to cytokeratin 5 and 18, androgen receptor (AR), and epidermal growth factor receptor (EGF-R) expression in tumor cells. Using semiquantitative reverse transcription-polymerase chain reaction, the amount of AR mRNA also was determined. In regressed and therapy-resistant prostate cancers, an increase in cytokeratin 5-positive tumor cells was noted when compared with untreated carcinomas. Similarly, the proportion of EGF-R-positive tumor cells increased in the treated cases, whereas the proportion of AR-positive tumor cells dropped in regressed carcinomas and increased in hormone-refractory cancers. In the latter group, an eightfold higher level of AR mRNA was observed when compared with the other cases. Changes in the proportion of cytokeratin 5 and EGF-R-positive tumor cells suggests that during androgen deprivation an enlarged subpopulation of tumor cells with combined features of basal and secretory phenotypes arises. The increased proportion of AR-positive tumor cells during the transition from the regression phase to the hormone escape phase points to an important role of AR overexpression in this process.
Gil-Diez de Medina
S
S
Groupe d'Etude des Tumeurs Urologiques, Centre de Recherches Chirurgicales, Hopital Henri Mondor, Créteil, France.
Salomon
L
L
Colombel
M
M
Abbou
C C
CC
Bellot
J
J
Thiery
J P
JP
Radvanyi
F
F
Van der Kwast
T H
TH
Chopin
D K
DK
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007633:Keratins / Q000378:metabolism*; D008297:Male; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D011944:Receptors, Androgen / Q000378:metabolism*
D012333:RNA, Messenger; D011944:Receptors, Androgen; D007633:Keratins; D066246:ErbB Receptors