Differential expression of S100A2 and S100A4 during progression of human prostate adenocarcinoma.

Purpose: To establish the clinical significance of calcium binding proteins S100A2 and S100A4 during progression of human prostate adenocarcinoma.

Patients And Methods: Expression pattern of S100A2 and S100A4 was determined in normal human prostate epithelial cells (NHPE); virally transformed prostate epithelial cells (PZ-HPV-7); several human prostate carcinoma cells (22Rv1, DU145, LNCaP, and PC3); tissue samples obtained during transuretheral prostatic resection from patients with benign prostate hyperplasia (BPH), prostatitis, and adenocarcinoma; and paraffin-embedded sections from pair-matched benign and cancer specimens of different tumor grade.

Results: High constitutive protein expression of S100A2 was observed in NHPE and PZ-HPV-7 cells, whereas its complete absence was observed in 22Rv1, DU145, LNCaP, and PC3 cells. Tissue samples of BPH and prostatitis exhibited higher mRNA and protein levels of S100A2 than low-grade cancer (Gleason score 6). Immunohistochemical analysis further confirmed high levels of S100A2 in benign tissues and a progressive loss with increasing tumor grade. The protein level of S100A4 was significantly higher in all carcinoma cells compared with NHPE and PZ-HPV-7 cells. The mRNA and protein level of S100A4 was significantly higher in high-grade cancer specimens compared with BPH, prostatitis, and low-grade cancer. The high levels of S100A4 observed in cancer tissue correlated with increasing tumor grade.

Conclusion: Loss of S100A2 and increased expression of S100A4 may be an important event during progression of prostate cancer in humans.