Prostate stem cell antigen is overexpressed in human transitional cell carcinoma

Nordine Amara, Ganesh S. Palapattu, Matthew Schrage, Zhennan Gu, George Thomas, Fred Dorey, Jonathan Said, Robert E. Reiter

Research output: Contribution to journalArticle

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Abstract

Prostate stem cell antigen (PSCA), a homologue of the Ly-6/Thy-1 family of cell surface antigens, is expressed by a majority of human prostate cancers and is a promising target for prostate cancer immunotherapy. In addition to its expression in normal and malignant prostate, we recently reported that PSCA is expressed at low levels in the transitional epithelium of normal bladder. In the present study, we compared the expression of PSCA in normal and malignant urothelial tissues to assess its potential as an immunotherapeutic target in transitional cell carcinoma (TCC). Immunohistochemical analysis of PSCA protein expression was performed on tissue sections from 32 normal bladder specimens, as well as 11 cases of low-grade transitional cell dysplasia, 21 cases of carcinoma in situ (CIS), 38 superficial transitional cell tumors (STCC, stages Ta-T1), 65 muscle-invasive TCCs (ITCCs, stages T2-T4), and 7 bladder cancer metastases. The level of PSCA protein expression was scored semiquantitatively by assessing both the intensity and frequency (i.e., percentage of positive tumor cells) of staining. We also examined PSCA mRNA expression in a representative sample of normal and malignant human transitional cell tissues. In normal bladder, PSCA immunostaining was weak and confined almost exclusively to the superficial umbrella cell layer. Staining in CIS and STCC was more intense and uniform than that seen in normal bladder epithelium (P < 0.001), with staining detected in 21 (100%) of 21 cases of CIS and 37 (97%) of 38 superficial tumors. PSCA protein was also detected in 42 (65%) of 65 of muscle-invasive and 4 (57%) of 7 metastatic cancers, with the highest levels of PSCA expression (i.e., moderate-strong staining in >50% of tumor cells) seen in 32% of invasive and 43% of metastatic samples. Higher levels of PSCA expression correlated with increasing tumor grade for both STCCs and ITCCs (P < 0.001). Northern blot analysis confirmed the immunohistochemical data, showing a dramatic increase in PSCA mRNA expression in two of five muscle-invasive transitional cell tumors when compared with normal samples. Confocal microscopy demonstrated that PSCA expression in TCC is confined to the cell surface. These data demonstrate that PSCA is overexpressed in a majority of human TCCs, particularly CIS and superficial tumors, and may be a useful target for bladder cancer diagnosis and therapy.

Original languageEnglish (US)
Pages (from-to)4660-4665
Number of pages6
JournalCancer Research
Volume61
Issue number12
StatePublished - Jun 15 2001
Externally publishedYes

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Transitional Cell Carcinoma
Prostate
Stem Cells
Antigens
Carcinoma in Situ
Urinary Bladder
Neoplasms
Urinary Bladder Neoplasms
Prostatic Neoplasms
Epithelium
Staining and Labeling
Muscles
Messenger RNA
Surface Antigens
Confocal Microscopy
Northern Blotting
Immunotherapy
Proteins

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Amara, N., Palapattu, G. S., Schrage, M., Gu, Z., Thomas, G., Dorey, F., ... Reiter, R. E. (2001). Prostate stem cell antigen is overexpressed in human transitional cell carcinoma. Cancer Research, 61(12), 4660-4665.

Prostate stem cell antigen is overexpressed in human transitional cell carcinoma. / Amara, Nordine; Palapattu, Ganesh S.; Schrage, Matthew; Gu, Zhennan; Thomas, George; Dorey, Fred; Said, Jonathan; Reiter, Robert E.

In: Cancer Research, Vol. 61, No. 12, 15.06.2001, p. 4660-4665.

Research output: Contribution to journalArticle

Amara, N, Palapattu, GS, Schrage, M, Gu, Z, Thomas, G, Dorey, F, Said, J & Reiter, RE 2001, 'Prostate stem cell antigen is overexpressed in human transitional cell carcinoma', Cancer Research, vol. 61, no. 12, pp. 4660-4665.
Amara N, Palapattu GS, Schrage M, Gu Z, Thomas G, Dorey F et al. Prostate stem cell antigen is overexpressed in human transitional cell carcinoma. Cancer Research. 2001 Jun 15;61(12):4660-4665.
Amara, Nordine ; Palapattu, Ganesh S. ; Schrage, Matthew ; Gu, Zhennan ; Thomas, George ; Dorey, Fred ; Said, Jonathan ; Reiter, Robert E. / Prostate stem cell antigen is overexpressed in human transitional cell carcinoma. In: Cancer Research. 2001 ; Vol. 61, No. 12. pp. 4660-4665.
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abstract = "Prostate stem cell antigen (PSCA), a homologue of the Ly-6/Thy-1 family of cell surface antigens, is expressed by a majority of human prostate cancers and is a promising target for prostate cancer immunotherapy. In addition to its expression in normal and malignant prostate, we recently reported that PSCA is expressed at low levels in the transitional epithelium of normal bladder. In the present study, we compared the expression of PSCA in normal and malignant urothelial tissues to assess its potential as an immunotherapeutic target in transitional cell carcinoma (TCC). Immunohistochemical analysis of PSCA protein expression was performed on tissue sections from 32 normal bladder specimens, as well as 11 cases of low-grade transitional cell dysplasia, 21 cases of carcinoma in situ (CIS), 38 superficial transitional cell tumors (STCC, stages Ta-T1), 65 muscle-invasive TCCs (ITCCs, stages T2-T4), and 7 bladder cancer metastases. The level of PSCA protein expression was scored semiquantitatively by assessing both the intensity and frequency (i.e., percentage of positive tumor cells) of staining. We also examined PSCA mRNA expression in a representative sample of normal and malignant human transitional cell tissues. In normal bladder, PSCA immunostaining was weak and confined almost exclusively to the superficial umbrella cell layer. Staining in CIS and STCC was more intense and uniform than that seen in normal bladder epithelium (P < 0.001), with staining detected in 21 (100{\%}) of 21 cases of CIS and 37 (97{\%}) of 38 superficial tumors. PSCA protein was also detected in 42 (65{\%}) of 65 of muscle-invasive and 4 (57{\%}) of 7 metastatic cancers, with the highest levels of PSCA expression (i.e., moderate-strong staining in >50{\%} of tumor cells) seen in 32{\%} of invasive and 43{\%} of metastatic samples. Higher levels of PSCA expression correlated with increasing tumor grade for both STCCs and ITCCs (P < 0.001). Northern blot analysis confirmed the immunohistochemical data, showing a dramatic increase in PSCA mRNA expression in two of five muscle-invasive transitional cell tumors when compared with normal samples. Confocal microscopy demonstrated that PSCA expression in TCC is confined to the cell surface. These data demonstrate that PSCA is overexpressed in a majority of human TCCs, particularly CIS and superficial tumors, and may be a useful target for bladder cancer diagnosis and therapy.",
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AU - Dorey, Fred

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AU - Reiter, Robert E.

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N2 - Prostate stem cell antigen (PSCA), a homologue of the Ly-6/Thy-1 family of cell surface antigens, is expressed by a majority of human prostate cancers and is a promising target for prostate cancer immunotherapy. In addition to its expression in normal and malignant prostate, we recently reported that PSCA is expressed at low levels in the transitional epithelium of normal bladder. In the present study, we compared the expression of PSCA in normal and malignant urothelial tissues to assess its potential as an immunotherapeutic target in transitional cell carcinoma (TCC). Immunohistochemical analysis of PSCA protein expression was performed on tissue sections from 32 normal bladder specimens, as well as 11 cases of low-grade transitional cell dysplasia, 21 cases of carcinoma in situ (CIS), 38 superficial transitional cell tumors (STCC, stages Ta-T1), 65 muscle-invasive TCCs (ITCCs, stages T2-T4), and 7 bladder cancer metastases. The level of PSCA protein expression was scored semiquantitatively by assessing both the intensity and frequency (i.e., percentage of positive tumor cells) of staining. We also examined PSCA mRNA expression in a representative sample of normal and malignant human transitional cell tissues. In normal bladder, PSCA immunostaining was weak and confined almost exclusively to the superficial umbrella cell layer. Staining in CIS and STCC was more intense and uniform than that seen in normal bladder epithelium (P < 0.001), with staining detected in 21 (100%) of 21 cases of CIS and 37 (97%) of 38 superficial tumors. PSCA protein was also detected in 42 (65%) of 65 of muscle-invasive and 4 (57%) of 7 metastatic cancers, with the highest levels of PSCA expression (i.e., moderate-strong staining in >50% of tumor cells) seen in 32% of invasive and 43% of metastatic samples. Higher levels of PSCA expression correlated with increasing tumor grade for both STCCs and ITCCs (P < 0.001). Northern blot analysis confirmed the immunohistochemical data, showing a dramatic increase in PSCA mRNA expression in two of five muscle-invasive transitional cell tumors when compared with normal samples. Confocal microscopy demonstrated that PSCA expression in TCC is confined to the cell surface. These data demonstrate that PSCA is overexpressed in a majority of human TCCs, particularly CIS and superficial tumors, and may be a useful target for bladder cancer diagnosis and therapy.

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