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

Oncogene volume 19, pages 1288–1296 (2000)Cite this article

Abstract

Prostate stem cell antigen (PSCA) is a recently defined 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 paraffin-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 quantified 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 identified 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.

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Acknowledgements

We thank Igor Vivanco and Connie Lin for technical assistance and Charles Sawyers and Doug Saffran for critical reading of the manuscript. We also thank Jean B deKernion for his support. This work was supported by grants from CaPCURE (RE Reiter, ON Witte and M Loda), National Institutes of Health Grant K08 CA74169 (RE Reiter), the STOP Cancer Foundation (RE Reiter) and the Cancer Research Institute (RE Reiter and ON Witte).

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Author notes

  1. Z Gu and G Thomas: Z Gu and G Thomas contributed equally to this work

Authors and Affiliations

  1. Department of Urology, University of California, Los Angeles, 90095, California, CA, USA

    Z Gu, G Thomas, J Yamashiro & RE Reiter

  2. Department of Pathology, University of California, Los Angeles, 90095, California, CA, USA

    G Thomas, I P Shintaku & JW Said

  3. Department of Orthopedics, University of California, Los Angeles, 90095, California, CA, USA

    F Dorey

  4. Urogenesys, Inc., Santa Monica, 90404, California, CA, USA

    A Raitano

  5. Department of Microbiology and Molecular Genetics, Molecular Biology Institute, Howard Hughes Medical Institute, University of California, Los Angeles, 90095, California, CA, USA

    ON Witte

  6. Department of Adult Oncology, Dana Farber Cancer Institute, Boston, 02115, Massachusetts, MA, USA

    M Loda

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Gu, Z., Thomas, G., Yamashiro, J. et al. Prostate stem cell antigen (PSCA) expression increases with high gleason score, advanced stage and bone metastasis in prostate cancer. Oncogene 19, 1288–1296 (2000). https://doi.org/10.1038/sj.onc.1203426

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