Prostate stem cell antigen (PSCA) expression increases with high gleason score, advanced stage and bone metastasis in prostate cancer

Prostate stem cell antigen (PSCA) is a recently defined homologue of the Th y-1/Ly-6 family of glycosylphosphatidylinositol (GPI)-anchored cell surface antigens, PSCA mRNA is expressed in the basal cells of normal prostate and in more than 80% of prostate cancers, The purpose of the present study was to examine PSCA protein expression in clinical specimens of human prostate cancer, Five monoclonal antibodies were raised against a PSCA-GST fusion p rotein and screened for their ability to recognize PSCA on the cell surface of human prostate cancer cells. Immunohistochemical analysis of PSCA expre ssion was performed on paraffin-embedded sections from 25 normal tissues, 1 12 primary prostate cancers and nine prostate cancers metastatic to bone. T he level of PSCA expression in prostate tumors was quantified and compared with expression in adjacent normal glands, The antibodies detect PSCA expre ssion on the cell surface of normal and malignant prostate cells and distin guish three extracellular epitopes on PSCA, Prostate and transitional epith elium reacted strongly with PSCA, PSCA staining was also seen in placental trophoblasts, renal collecting duets and neuroendocrine cells in the stomac h and colon, All other normal tissues tested were negative. PSCA protein ex pression was identified in 105/112 (94%) primary prostate tumors and 9/9 (1 00%) bone metastases, The level of PSCA expression increased with higher Gl eason score (P = 0.016), higher tumor stage (P = 0.010) and progression to androgen-independence (P = 0.021). Intense, homogeneous staining was seen i n all nine bone metastases. PSCA is a cell surface protein with limited exp ression in extraprostatic normal tissues, PSCA expression correlates with t umor stage, grade and androgen independence and may have prognostic utility . Because expression on the surface of prostate cancer cells increases with tumor progression, PSCA may be a useful molecular target in advanced prost ate cancer.