Prostate-specific membrane antigen expression in normal and malignant human tissues.
Prostate-specific membrane antigen expression in normal and malignant human tissues.
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发表时间：
1997
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通讯作者：
David A. Silver;Inmaculada Pellicer;W. Fair;W. Heston;C. Cordon-Cardo
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作者：
David A. Silver;Inmaculada Pellicer;W. Fair;W. Heston;C. Cordon-Cardo
前列腺特异性膜抗原是前列腺上皮产生的具有叶酸水解酶活性的II型膜蛋白。该分子在前列腺外组织（包括小肠和脑）中的表达也有记录。在本研究中，我们对一组特征明确的正常和恶性人体组织进行了广泛的免疫组织化学分析，以进一步确定前列腺特异性膜抗原（PSMA）的表达模式。前列腺上皮、十二指肠黏膜和近端肾小管的一个亚群中检测到PSMA水平。结肠隐窝中的神经内分泌细胞亚群也表现出PSMA免疫反应性。所有其他正常组织，包括大脑皮层和小脑，都没有检测到PSMA的水平。35例原发性前列腺腺癌中的33例和8例淋巴结转移中的7例显示肿瘤细胞PSMA免疫染色。18例转移至骨的前列腺肿瘤中有8例表达PSMA。所有其他研究的非前列腺原发肿瘤均未检测到PSMA水平。然而，某些恶性肿瘤的瘤周和瘤内毛细血管内皮细胞染色强烈，包括17例肾细胞癌中的8例，13例移行细胞癌中的7例，19例结肠癌中的3例。前列腺外PSMA的表达似乎受到高度限制。然而，其不同的解剖分布暗示了比以前怀疑的更广泛的功能意义。在晚期前列腺癌中发现PSMA免疫反应性的降低表明该分子的表达可能与肿瘤分化程度有关。PSMA在某些肿瘤毛细血管床内皮细胞中的新表达可能与肿瘤血管生成有关，并提示了特异性靶向肿瘤新生血管的潜在机制。
Prostate-specific membrane antigen is a type II membrane protein with folate hydrolase activity produced by prostatic epithelium. The expression of this molecule has also been documented in extraprostatic tissues, including small bowel and brain. In the present study, an extensive immunohistochemical analysis was performed on a panel of well-characterized normal and malignant human tissues to further define the pattern of prostate-specific membrane antigen (PSMA) expression. Detectable PSMA levels were identified in prostatic epithelium, duodenal mucosa, and a subset of proximal renal tubules. A subpopulation of neuroendocrine cells in the colonic crypts also exhibited PSMA immunoreactivity. All other normal tissues, including cerebral cortex and cerebellum, had undetectable levels of PSMA. Thirty-three of 35 primary prostate adenocarcinomas and 7 of 8 lymph node metastases displayed tumor cell PSMA immunostaining. Eight of 18 prostate tumors metastatic to bone expressed PSMA. All of the other nonprostatic primary tumors studied had undetectable PSMA levels. However, intense staining was observed in endothelial cells of capillary vessels in peritumoral and endotumoral areas of certain malignancies, including 8 of 17 renal cell carcinomas, 7 of 13 transitional cell carcinomas, and 3 of 19 colon carcinomas. Extraprostatic PSMA expression appears to be highly restricted. Nevertheless, its diverse anatomical distribution implies a broader functional significance than previously suspected. The decrease in PSMA immunoreactivity noted in advanced prostate cancer suggests that expression of this molecule may be linked to the degree of tumor differentiation. The neoexpression of PSMA in endothelial cells of capillary beds in certain tumors may be related to tumor angiogenesis and suggests a potential mechanism for specific targeting of tumor neovasculature.