Basic scienceMetastatic renal cell carcinoma neovasculature expresses prostate-specific membrane antigen☆
Section snippets
Tissue specimens and antibodies
Formalin-fixed, paraffin-embedded tissue samples from patients were randomly obtained from the Memorial Sloan-Kettering Cancer Center institutional tissue bank. Cytogen provided the 7E11 mAb. The mAb PM2J004.5 was provided by Hybritech (San Diego, Calif). The anti-endothelial cell mAb CD34 (Immunotech, Coulter, Opa Locka, Fla) was used for comparative immunohistochemical reactions in the cancerous tissue types.
Immunohistochemistry
One representative formalin-fixed, paraffin-embedded tumor-bearing tissue block was
Metastatic conventional (clear cell) renal carcinoma
We examined various sites of metastatic conventional (clear cell) renal carcinoma (Table I). In these different metastatic locations, the tumor-associated neovasculature of the metastatic conventional (clear cell) renal carcinoma consistently expressed PSMA. The immunoreactions of the anti-PSMA mAbs with the endothelial cells of the neovasculature were confirmed by similar staining by the anti-CD34 mAb, which was consistently positive in the neovascular endothelial cells (Fig. 1). The renal
Comment
The results of our study confirm PSMA expression in the neovasculature of metastatic renal cell carcinoma. Previous studies have examined primary tumor neovasculature expression of PSMA. Silver et al.24 demonstrated 7E11 binding and “neoexpression of PSMA in endothelial cells” in a limited subset of tumors, including renal cell carcinoma (unspecified type), transitional cell carcinoma of the urinary bladder, and colonic adenocarcinoma. More recently, we examined multiple anti-PSMA antibodies
Conclusions
As in primary prostate carcinoma, the neovasculature of metastatic prostate carcinoma, regardless of metastatic site, rarely express PSMA. The neovascular endothelial cells of metastatic conventional (clear cell) renal carcinoma, however, consistently express PSMA. This metastatic tumor-associated neovascular expression may prove useful for future antibody-based diagnosis and therapy.
References (29)
- et al.
Mapping, genomic organization and promoter analysis of the human prostate-specific membrane antigen gene
Biochim Biophys Acta
(1998) - et al.
Expression of prostate-specific membrane antigen in normal, benign and malignant prostate tissues
Urol Oncol
(1995) - et al.
Upregulation of prostate-specific membrane antigen after androgen-deprivation therapy
Urology
(1996) - et al.
Radioimmunoscintigraphy of pelvic lymph nodes with 111indium-labeled monoclonal antibody CYT-356
J Urol
(1994) - et al.
Radioimmunoscintigraphy with 111indium labeled CYT-356 for the detection of occult prostate cancer recurrence
J Urol
(1994) - et al.
111Indium-capromab pendetide in the evaluation of patients with residual or recurrent prostate cancer after radical prostatectomy
J Urol
(1998) - et al.
CD34 immunohistochemical assessment of angiogenesis as a prognostic marker for prostate cancer recurrence after radical prostatectomy
J Urol
(1998) - et al.
Angiogenesis and metastasis
Eur J Cancer
(1996) - et al.
Indium-capromab pendetide unexpectedly localizes to renal cell carcinoma
J Urol
(1999) - et al.
Monoclonal antibodies to a new antigenic marker in epithelial cells and serum of prostatic cancer patients
Anticancer Res
(1987)
Molecular cloning of a complementary DNA encoding a prostate-specific membrane antigen
Cancer Res
Prostate-specific membrane antigena novel folate hydrolase in human prostatic carcinoma cells
Clin Cancer Res
Prostate-specific membrane antigen is a hydrolase with substrate and pharmacologic characteristics of a neuropeptidase
Proc Natl Acad Sci USA
Molecular characterization of human brain n-acetylated alpha-linked acidic dipeptidase (NAALADase)
J Pharmacol Exp Ther
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This work was supported by grants from the NIH, NIDDKD/NCI 47650, and CaP CURE.
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Dr. Heston’s current address is Department of Urology, Cleveland Clinic Foundation, Cleveland, OH 44195.