Androgen receptors are differentially expressed in Gleason patterns of prostate cancer and down-regulated in matched lymph node metastases.
BACKGROUND
Androgen receptor (AR) expression profile in the different Gleason patterns (GP) of primary prostate cancers and nodal metastases is unknown. More information about AR distribution is needed to optimize evaluation methods and to better understand the role of AR in development and progression of prostate cancer.


METHODS
A tissue microarray was constructed from 119 hormone-naïve nodal positive, surgically treated prostate cancers containing tissues from all GP present in every primary tumor and the matched metastases. ARs were evaluated immunohistochemically and an expression score (intensity × percentage of positive cells) was assigned for each tissue spot.


RESULTS
ARs were up-regulated in primary tumors compared to normal glands and significantly different expressed in the GP (mean AR scores: GP 3=128.7, GP 4=159.1, GP 5=123.5; P=0.016). A similar expression profile was observed in metastases, however, on significantly (P<0.001) lower level (mean AR scores: GP 3=70.5, GP 4=90.4, GP 5=71.7; P=0.114). High AR expression in metastases was associated with larger total size of metastases (P=0.008). All other correlations of AR expression in primary tumors and metastases with quantitative (age, prostate cancer volume, number of metastases) or categorical (tumor stage, Gleason score of the primary tumor and metastases) tumor characteristics or with survival were insignificant.


CONCLUSIONS
ARs are differentially expressed in GP what should be considered in prognostic models which include AR. In nodal metastases, ARs are significantly down-regulated suggesting decreased dependence on androgens already under hormone-naïve conditions. AR expression level is not prognostic in nodal positive disease.
Fleischmann
Achim
A
Institute of Pathology, University of Bern, Bern, Switzerland. achim.fleischmann@pathology.unibe.ch
Rocha
Carla
C
Schobinger
Sylviane
S
Seiler
Roland
R
Wiese
Birgitt
B
Thalmann
George N
GN
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000368:Aged; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D011944:Receptors, Androgen / Q000096:biosynthesis* / Q000235:genetics; D018709:Statistics, Nonparametric; D046888:Tissue Array Analysis
C410798:AR protein, human; D011944:Receptors, Androgen