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

Abstract

Prostate stem cell antigen (PSCA) is a recently de®ned homologue of the Thy-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 protein and screened for their ability to recognize PSCA on the cell surface of human prostate cancer cells. Immunohistochemical analysis of PSCA expression was performed on paran-embedded sections from 25 normal tissues, 112 primary prostate cancers and nine prostate cancers metastatic to bone. The level of PSCA expression in prostate tumors was quanti®ed and compared with expression in adjacent normal glands. The antibodies detect PSCA expression on the cell surface of normal and malignant prostate cells and distinguish three extracellular epitopes on PSCA. Prostate and transitional epithelium reacted strongly with PSCA. PSCA staining was also seen in placental trophoblasts, renal collecting ducts and neuroendocrine cells in the stomach and colon. All other normal tissues tested were negative. PSCA protein expression was identi®ed in 105/112 (94%) primary prostate tumors and 9/9 (100%) bone metastases. The level of PSCA expression increased with higher Gleason score (P=0.016), higher tumor stage (P=0.010) and progression to androgen-independence (P=0.021). Intense, homogeneous staining was seen in all nine bone metastases. PSCA is a cell surface protein with limited expression in extraprostatic normal tissues. PSCA expression correlates with tumor 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 prostate cancer.

Improving Chimeric Antigen Receptor-Modified T Cell Function by Reversing the Immunosuppressive Tumor Microenvironment of Pancreatic Cancer

“…This is particularly noteworthy given that PSCA has been shown to be expressed at low levels in some normal tissues. 9,25 Pancreatic cancer remains the fourth leading cause of cancer-related mortality in the USA with a 5-year overall survival of <5%. 26 More than 53,070 patients are diagnosed annually, and an estimated 41,780 individuals die from this disease each year.…”

Vaccination of advanced prostate cancer patients with PSCA and PSA peptide‐loaded dendritic cells induces DTH responses that correlate with superior overall survival

“…This 123-aa type 1 membrane protein has a high tissue specificity and is expressed on more than 85% of CaP specimens, with expression levels increasing with higher Gleason scores and androgen independence. [11][12][13] Several PSCA-derived, HLA-A*0201 restricted peptides have been identified that may be recognized by antigen-specific T cells in vitro. 14,15 Since PSCA is not shedded from the cell membrane, we hypothesized that it may be the most promising CaP-associated antigen for DC-based immunization.…”

Molecular markers and determinants of prostate cancer metastasis

“…Preliminary analysis of archival specimens showed a high percentage of positive staining with an antisense RNA probe for samples, showing overt cancer pathology or indications of high grade PIN, while corresponding normal sections stained weakly (Reiter et al, 1998). Follow-up work using a series of monoclonal antibodies report that an expanded clinical study showed a strong correlation of increased PSCA expression with higher Gleason grade and bone metastasis (Gu et al, 2000). This work indicated that expression was also detected in secretory epithelial cells possibly as a carryover during differentiation of basal into secretory cell populations.…”