ANDROGEN RECEPTOR STATUS IN LOCALIZED AND LOCALLY PROGRESSIVE HORMONE-REFRACTORY HUMAN PROSTATE-CANCER

Heterogeneity in human androgen receptor (hAR) expression in prostate cancer is considered to be implicated in tumor progression. hAR expres sion was therefore studied immunohistochemically in localized and loca lly progressive, hormone refractory (HR) prostate cancer. Because alte red functional activity of the hAR may be dire to changes in the struc tural integrity, of the hAR gene, exons 2 to 8 of the hAR gene were as sessed for mutations by single-strand conformation polymorphism (SSCP) analysis and exon 1 was analyzed for the size of the CAG repeat. The hormone binding capacity, a prerequisite for ligand-regulated receptor function, was determined by a ligand binding assay. Coexpression of t he hAR and prostate-specific antigen (PSA) was studied by a sequential double immunoenzymatic staining to verify whether PSA expression is a parameter of hAR function. Almost all human prostatic carcinomas reve aled heterogeneous hAR expression, regardless of tumor differentiation and progression. Putative predominance of hAR-negative tumor areas in HR prostate cancer teas not observed. No hAR gene mutations or major changes in the CAG repeat were found in the 18 HR carcinomas or in the 3 control samples. Moreover, all selected hAR-expressing cancers were able to bind the synthetic androgen methyltrienolone (R1881). Immunoe nzymatic double staining revealed even PSA expression in hAR-negative tumor areas. PSA immunohistochemistry in human prostatic carcinomas th erefore is of no use in determining hAR fucntional activity. Thus, mos t prostatic carcinomas, even when progressed to a state of hormone ins ensitivity, contain a structurally intact hAR gene, heterogeneously ex pressed with retained androgen binding capacity.