Lynch D F, Hassen W, Clements M A, Schellhammer P F, Wright G L
Department of Urology, Eastern Virginia Medical School, Norfolk, USA.
Prostate. 1997 Aug 1;32(3):214-20. doi: 10.1002/(sici)1097-0045(19970801)32:3<214::aid-pros8>3.0.co;2-k.
Tumorigenesis and progression to metastatic disease are accompanied by changes in the expression of cell adhesion molecules (CAMs). Normally expressed CAMs, such as E-cadherin, are lost, while others, i.e., ICAM-1, VCAM-1, NCAM, and E-selectin, are altered and overexpressed in progressive disease and metastases. Abnormal levels of these latter CAMs have been observed in melanoma and carcinomas of the colon 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 with benign prostate hypertrophy (BPH) from those with prostate carcinoma (CaP) and identify prostate cancers with high potential for progression to metastatic disease.
Serum levels of these CAMs were determined by ELISA in serum from normal males and females and from patients with BPH and CaP before and after treatment. Sera from patients with breast carcinoma, colon carcinoma, melanoma, and small-cell lung carcinoma were also evaluated, as soluble CAMs have been reported to be elevated in these cancer patients.
ICAM-1 levels were elevated in sera from patients with breast carcinoma (P = 0.0004) and melanoma (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 of patients with SCLC (P = 0.0001). Normal levels of ICAM-1, E-selectin, and NCAM were found in both BPH and pretreatment CaP patients. Median NCAM levels in hormone-refractive CaP patients were significantly greater than in BPH (P = 0.0005) and CaP patients with pathologically determined organ-confined (P = 0.0014) or nonorgan-confined disease (P = 0.0385). VCAM-1 levels were significantly elevated in both BPH patients (P = 0.0002) and CaP patients (P = 0.0002) when compared with levels 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.
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 progression, for identifying metastatic potential, or for monitoring treatment.
肿瘤发生及进展为转移性疾病的过程伴随着细胞黏附分子（CAMs）表达的变化。正常表达的CAMs，如E-钙黏蛋白，会丢失，而其他一些分子，即细胞间黏附分子-1（ICAM-1）、血管细胞黏附分子-1（VCAM-1）、神经细胞黏附分子（NCAM）和E-选择素，在疾病进展和转移过程中会发生改变并过度表达。在黑色素瘤、结肠癌和乳腺癌中已观察到这些后期CAMs的异常水平，且NCAM在小细胞肺癌（SCLC）中过度表达。本研究的目的是确定血清中ICAM-1、VCAM-1、NCAM和E-选择素水平能否区分良性前列腺增生（BPH）患者和前列腺癌（CaP）患者，并识别具有高转移疾病进展潜力的前列腺癌。
通过酶联免疫吸附测定（ELISA）法测定正常男性和女性以及BPH和CaP患者治疗前后血清中这些CAMs的水平。还评估了乳腺癌、结肠癌、黑色素瘤和小细胞肺癌患者的血清，因为据报道这些癌症患者中可溶性CAMs水平升高。
乳腺癌患者（P = 0.0004）和黑色素瘤患者（P = 0.0001）血清中的ICAM-1水平升高。结肠癌患者（P = 0.0001）血清中的VCAM-1水平升高。小细胞肺癌患者血清中的NCAM水平升高（P = 0.0001）。在BPH患者和CaP治疗前患者中均发现ICAM-1、E-选择素和NCAM水平正常。激素难治性CaP患者的NCAM水平中位数显著高于BPH患者（P = 0.0005）以及病理确定为器官局限性（P = 0.0014）或非器官局限性疾病（P = 0.0385）的CaP患者。与年龄匹配的正常供体水平相比，BPH患者（P = 0.0002）和CaP患者（P = 0.0002）的VCAM-1水平均显著升高。在确定性放疗、根治性前列腺切除术或激素治疗后监测CaP患者时，未发现任何一种CAMs比前列腺特异性抗原（PSA）更具优势。
本研究结果表明，血清ICAM-1、VCAM-
