Published in Cancer Detection and Prevention 2000; 24(6):579-588.

Detection of Prostate-Specific Membrane Antigen Expressing Cells in Blood Obtained from Renal Cancer Patients: A Potential Biomarker of Vascular Invasion

Alexandre de Ia Thille, MD,a Yichen Cao,a Ihor S. Sawczuk, MD,a Thnji Nozemu, MD,b Vivette d’Agati, MD,b James M. McKiernan, MD,a Emilia Bagiella, PhD,c Ralph Buttyan, PhD,a,b Martin Burchardt, MD,a Carl A. Qisson, MD,a Neil Bander, MD,d and Aaron E. Katz, MDa

Squier Urological Clinic and Departments of aUrology and bPathology and cDivision of Biostatistics, College of Physicians and Surgeons of Columbia University, New York; and dDepartment of Urology, Cornell University School of Medicine, New York, NY

Address all correspondence and reprint requests to: Ralph Buttyan, PhD, Columbia-Presbyterian Medical Center, Atchley Pavilion, Eleventh Floor, Room 1153, 161 Fort Washington Avenue, New York, NY 10032

ABSTRACT: Originally, prostate-specific membrane antigen (PSMA) was described in benign and malignant prostate cells. On the basis of recent reports that this antigen also is expressed in normal renal proximal tubular cells and in the neovascular endothelium associated with renal carcinoma, we used a nested reverse transcriptase—polymerase chain reaction assay to evaluate whether PSMA-expressing cells might be present in specimens of peripheral blood obtained from renal cancer patients, benign renal tumor patients, and healthy volunteers. Our reverse transcriptase—polymerase chain reaction PSMA assay had a sensitivity of detecting 1 lymph node prostate cancer (LNCaP) per 107 lymphocytes. None of the 20 non—renal cancer controls were positive for PSMA mRNA, whereas 11 of 50 patients (22%) with diagnosed renal cancer were positive. Despite a comparative increase of PSMA positivity with stage, no statistical correlation was found. However, 44% of PSMA-positive patients had tumor size greater than 12 cm, versus only 9% in patients negative for PSMA (P = .03), and 67% of positive PSMA patients were found to have vascular invasion versus only 16% of patients negative for PSMA (P = .006; odds ratio, 10.8). This preliminary study suggests the possibility that PSMA expression in peripheral blood might be a useful biomarker for detecting or monitoring the progression of renal cancer in patients.

KEY WORDS: prostate-specific membrane antigen, renal cancer, reverse transcriptase-polymerase chain reaction, vascular invasion.