This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Amara, N. Articles by Reiter, R. E. Search for Related Content PubMed PubMed Citation Articles by Amara, N. Articles by Reiter, R. E.

Prostate Stem Cell Antigen Is Overexpressed in Human Transitional Cell Carcinoma¹

Departments of Urology [N. A., G. S. P., Z. G., R. E. R.], Pathology [M. S., G. V. T., J. S.], and Orthopedics [F. D.], and Jonsson Cancer Center [N. A., G. S. P., Z. G., R. E. R.], University of California-Los Angeles School of Medicine, Los Angeles, California 90095

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 T_a-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.

This article has been cited by other articles:

				J. F. Mushinski, P. Nguyen, L. M. Stevens, C. Khanna, S. Lee, E. J. Chung, M.-J. Lee, Y. S. Kim, W. M. Linehan, M. A. Horisberger, et al. Inhibition of Tumor Cell Motility by the Interferon-inducible GTPase MxA J. Biol. Chem., May 29, 2009; 284(22): 15206 - 15214. [Abstract] [Full Text] [PDF]

				J. V. Leyton, T. Olafsen, E. J. Lepin, S. Hahm, K. B. Bauer, R. E. Reiter, and A. M. Wu Humanized Radioiodinated Minibody For Imaging of Prostate Stem Cell Antigen-Expressing Tumors Clin. Cancer Res., November 15, 2008; 14(22): 7488 - 7496. [Abstract] [Full Text] [PDF]

				Z. Gu, J. Yamashiro, E. Kono, and R. E. Reiter Anti-Prostate Stem Cell Antigen Monoclonal Antibody 1G8 Induces Cell Death In vitro and Inhibits Tumor Growth In vivo via a Fc-Independent Mechanism Cancer Res., October 15, 2005; 65(20): 9495 - 9500. [Abstract] [Full Text] [PDF]

				T. Nakamoto, H. Okada, T. Nakajima, A. Ikuta, K. Yasuda, and H. Kanzaki Progesterone induces the fibulin-1 expression in human endometrial stromal cells Hum. Reprod., June 1, 2005; 20(6): 1447 - 1455. [Abstract] [Full Text] [PDF]

				J. S. Lam, J. Yamashiro, I. P. Shintaku, R. L. Vessella, R. B. Jenkins, S. Horvath, J. W. Said, and R. E. Reiter Prostate Stem Cell Antigen Is Overexpressed in Prostate Cancer Metastases Clin. Cancer Res., April 1, 2005; 11(7): 2591 - 2596. [Abstract] [Full Text] [PDF]

				Z. Zhigang and S. Wenlv Prostate Stem Cell Antigen (PSCA) Expression in Human Prostate Cancer Tissues: Implications for Prostate Carcinogenesis and Progression of Prostate Cancer Jpn. J. Clin. Oncol., July 1, 2004; 34(7): 414 - 419. [Abstract] [Full Text] [PDF]

				J. P.T. Higgins, L. Wang, N. Kambham, K. Montgomery, V. Mason, S. U. Vogelmann, K. V. Lemley, P. O. Brown, J. D. Brooks, and M. van de Rijn Gene Expression in the Normal Adult Human Kidney Assessed by Complementary DNA Microarray Mol. Biol. Cell, February 1, 2004; 15(2): 649 - 656. [Abstract] [Full Text] [PDF]

				A. Jain, A. Lam, I. Vivanco, M. F. Carey, and R. E. Reiter Identification of an Androgen-Dependent Enhancer within the Prostate Stem Cell Antigen Gene Mol. Endocrinol., October 1, 2002; 16(10): 2323 - 2337. [Abstract] [Full Text] [PDF]

				S. Ross, S. D. Spencer, I. Holcomb, C. Tan, J. Hongo, B. Devaux, L. Rangell, G. A. Keller, P. Schow, R. M. Steeves, et al. Prostate Stem Cell Antigen as Therapy Target: Tissue Expression and in Vivo Efficacy of an Immunoconjugate Cancer Res., May 1, 2002; 62(9): 2546 - 2553. [Abstract] [Full Text] [PDF]

				T. Watabe, M. Lin, H. Ide, A. A. Donjacour, G. R. Cunha, O. N. Witte, and R. E. Reiter Growth, regeneration, and tumorigenesis of the prostate activates the PSCA promoter PNAS, January 8, 2002; 99(1): 401 - 406. [Abstract] [Full Text] [PDF]