SERUM LEVELS OF ENDOTHELIAL AND NEURAL CELL-ADHESION MOLECULES IN PROSTATE-CANCER

BACKGROUND. Tumorigenesis and progression to metastatic disease are ac companied by changes in the expression of cell adhesion molecules (CAM s). Normally expressed CAMs, such as E-cadherin, are lost, while other s, i.e., ICAM-1, VCAM-1, NCAM, and E-selectin, are altered and overexp ressed in progressive disease and metastases. Abnormal levels of these latter CAMs have been observed in melanoma and carcinomas of the colo n and breast, and NCAM is overexpressed in small-cell lung carcinoma ( SCLC). The objective of this study was to determine if serum levels of ICAM-1, VCAM-1, NCAM, and E-selectin could differentiate patients wit h benign prostate hypertrophy (BPH) from those with prostate carcinoma (CaP) and identify prostate cancers with high potential for progressi on to metastatic disease. METHODS. Serum levels of these CAMs were det ermined by ELISA in serum from normal males and females and from patie nts with BPH and CaP before and after treatment. Sera from patients wi th breast carcinoma, colon carcinoma, melanoma, and small-cell lung ca rcinoma were also evaluated, as soluble CAMs have been reported to be elevated in these cancer patients. RESULTS. ICAM-1 levels were elevate d in sera from patients with breast carcinoma (P = 0.0004) and melanom a (P = 0.0001). VCAM-1 levels were elevated in sera from patients with colon carcinoma (P = 0.0001). NCAM levels were elevated in the sera o f patients with SCLC (P = 0.0001). Normal levels of ICAM-1, E-selectin , and NCAM were found in both BPH and pretreatment CaP patients. Media n NCAM levels in hormone-refractive CaP patients were significantly gr eater than in BPH (P = 0.0005) and CaP patients with pathologically de termined organ-confined (P = 0.0014) or nonorgan-confined disease (P = 0.0385). VCAM-1 levels were significantly elevated in both BPH patien ts (P = 0.0002) and CaP patients (P = 0.0002) when compared with level s for normal age-matched donors. None of the CAMs were found to offer an advantage over prostatic-specific antigen (PSA) for monitoring CaP patients following definitive radiotherapy, radical prostatectomy, or hormonal therapy. CONCLUSIONS. The results of this study indicate that serum ICAM-1, VCAM-1, NCAM, and E-selectin are not clinically useful biomarkers for differentiating CaP from BPH, for predicting progressio n, for identifying metastatic potential, or for monitoring treatment. (C) 1997 Wiley-Liss, Inc.