Elsevier

Urology

Volume 57, Issue 4, April 2001, Pages 801-805
Urology

Basic science
Metastatic renal cell carcinoma neovasculature expresses prostate-specific membrane antigen

https://doi.org/10.1016/S0090-4295(00)01094-3Get rights and content

Abstract

Objectives. To determine whether the tumor-associated neovasculature of metastatic prostate and metastatic conventional (clear cell) renal carcinoma express prostate-specific membrane antigen (PSMA). PSMA is a type II integral membrane glycoprotein highly expressed in prostate cancer cells and also recently discovered to be expressed in the neovasculature of non-prostatic primary malignancies.

Methods. We examined metastatic prostate carcinoma (22 patients) and metastatic conventional (clear cell) renal carcinoma (20 patients) in various anatomic sites, including bone, lymph nodes, liver, lung, and soft tissue. Using the biotin-streptavidin method, we performed immunohistochemical reactions with the anti-PSMA monoclonal antibodies (mAbs) 7E11 and PM2J004.5 and with the anti-endothelial cell mAb CD34.

Results. Metastatic conventional (clear cell) renal carcinoma consistently expressed PSMA. The PM2J004.5 mAb was positive in 20 of 20 specimens, and the 7E11 mAb was positive in 15 of 20. The anti-PSMA immunoreactions with the neovasculature were confirmed by similar staining by the anti-CD34 mAb (20 of 20). Although the metastatic prostatic cancer cells expressed PSMA in all the specimens, only 2 of 22 had neovasculature PSMA expression.

Conclusions. As in primary prostatic adenocarcinomas, the neovasculature of metastatic prostate cancer, regardless of site, rarely express PSMA. The neovascular endothelial cells of metastatic clear cell renal carcinoma, however, express PSMA. This expression may make PSMA an effective target for mAb-based antineovasculature therapy in metastatic renal carcinoma.

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.

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  • Cited by (0)

    This work was supported by grants from the NIH, NIDDKD/NCI 47650, and CaP CURE.

    1

    Dr. Heston’s current address is Department of Urology, Cleveland Clinic Foundation, Cleveland, OH 44195.

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