Differential Expression of Genes Related to Androgen and Estrogen Metabolism in Hereditary versus Sporadic Prostate Cancer

Abstract

The hereditary predisposition to prostate cancer is rare and accounts for <5% of cases. Except for younger age at diagnosis, no phenotypic features have been clearly associated with hereditary prostate cancer. The aim of the study was to analyze the expression of genes related to androgen and estrogen metabolism in both hereditary and sporadic prostate cancers in patients matched for clinicopathologic features. Tissues were obtained from patients included in a national familial prostate cancer registry. From the 120 cases of hereditary forms suggesting autosomal dominant Mendelian inheritance, 21 patients were treated by radical prostatectomy for whom formalin-fixed tissue was available. Twenty-one sporadic cases were then matched according to age, Gleason score, and pathologic stage. Immunohistochemistry was done on tissue microarray using antibodies directed against androgen receptor (AR), estrogen receptor alpha (ERA), estrogen receptor beta, 5alpha-reductase I and II, aromatase, and the proliferation marker Ki67. The percentage of AR-positive cancer cells was higher in hereditary cancer compared with sporadic cases (P < 0.004). In contrast, the mean number of ERA-positive stromal cells was lower in hereditary versus sporadic cancer (P < 0.03). This differential expression of AR and ERA suggests that a specific pattern of hormone receptors is associated with hereditary predisposition to prostate cancer.