Her-2-neu expression and progression toward androgen independence in humanprostate cancer

Background: Human prostate cancers are initially androgen dependent but ult imately become androgen independent. Overexpression of the Her-2-neu recept or tyrosine kinase has been associated with the progression to androgen ind ependence in prostate cancer cells. Ne examined the expression of Her-2-neu in normal and cancerous prostate tissues to assess its role in the progres sion to androgen independence. Methods: Prostate cancer tissue sections wer e obtained from 67 patients treated by surgery alone (UNT tumors), 34 patie nts treated with total androgen ablation therapy before surgery (TAA tumors ), and 18 patients in whom total androgen ablation therapy failed and who d eveloped bone metastases (androgen-independent [A1] disease). The sections were immunostained for Her-2-neu, androgen receptor (AR), prostate-specific antigen (PSA), and Ki-67 (a marker of cell proliferation) protein expressi on. Messenger RNA (mRNA) levels and gene amplification of Her-2-neu were ex amined by RNA in situ hybridization and fluorescent ill situ hybridization( FISH), respectively, in a subset of 27 tumors (nine UNT, 11 TAA, and seven AI), All statistical tests were two-sided. Results: Her-2-neu protein expre ssion was statistically significantly higher in TAA. tumors than in UNT tum ors with the use of two different scoring methods (P = .008 and P = .002), The proportion of Her-2-neu-positive tumors increased from the UNT group (1 7 of 67) to the TAA group (20 of 34) to the AI group (14 of 18) (P<.001). W hen compared with UNT tumors, tumor cell proliferation was higher in Al tum ors (P = .014) and lower in TAA tumors (P<.001). All tumors expressed AR an d PSA proteins. Although Her-2-neu mRNA expression was high in TAA and AI t umors, no Her-2-neu gene amplification was detected by FISH in any of the t umor types. Conclusions: Her-2-neu expression appears to increase with prog ression to androgen independence. Thus, therapeutic targeting of this tyros ine kinase in prostate cancer may be warranted.