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

Z. Gu, George Thomas, J. Yamashiro, I. P. Shintaku, F. Dorey, A. Raitano, O. N. Witte, J. W. Said, M. Loda, R. E. Reiter

Research output: Contribution to journalArticle

305 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1288-1296
Number of pages9
JournalOncogene
Volume19
Issue number10
StatePublished - Mar 2 2000
Externally publishedYes

Fingerprint

Neoplasm Grading
Prostate
Prostatic Neoplasms
Stem Cells
Neoplasm Metastasis
Antigens
Bone and Bones
Neoplasms
Surface Antigens
Androgens
Staining and Labeling
Neuroendocrine Cells
Glycosylphosphatidylinositols

Keywords

  • Antibody
  • Neoplasm
  • Prostate
  • Prostate stem cell antigen (PSCA)

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Gu, Z., Thomas, G., Yamashiro, J., Shintaku, I. P., Dorey, F., Raitano, A., ... Reiter, R. E. (2000). Prostate stem cell antigen (PSCA) expression increases with high gleason score, advanced stage and bone metastasis in prostate cancer. Oncogene, 19(10), 1288-1296.

Prostate stem cell antigen (PSCA) expression increases with high gleason score, advanced stage and bone metastasis in prostate cancer. / Gu, Z.; Thomas, George; Yamashiro, J.; Shintaku, I. P.; Dorey, F.; Raitano, A.; Witte, O. N.; Said, J. W.; Loda, M.; Reiter, R. E.

In: Oncogene, Vol. 19, No. 10, 02.03.2000, p. 1288-1296.

Research output: Contribution to journalArticle

Gu, Z, Thomas, G, Yamashiro, J, Shintaku, IP, Dorey, F, Raitano, A, Witte, ON, Said, JW, Loda, M & Reiter, RE 2000, 'Prostate stem cell antigen (PSCA) expression increases with high gleason score, advanced stage and bone metastasis in prostate cancer', Oncogene, vol. 19, no. 10, pp. 1288-1296.
Gu, Z. ; Thomas, George ; Yamashiro, J. ; Shintaku, I. P. ; Dorey, F. ; Raitano, A. ; Witte, O. N. ; Said, J. W. ; Loda, M. ; Reiter, R. E. / Prostate stem cell antigen (PSCA) expression increases with high gleason score, advanced stage and bone metastasis in prostate cancer. In: Oncogene. 2000 ; Vol. 19, No. 10. pp. 1288-1296.
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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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