Expression of prostate-specific membrane antigen in normal, benign, and malignant prostate tissues.
Expression of prostate-specific membrane antigen in normal, benign, and malignant prostate tissues.
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DOI：
10.1016/1078-1439(95)00002-y
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发表时间：
1995-01-01
期刊：
影响因子：
--
通讯作者：
Schellhammer, P F
中科院分区：
文献类型：
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作者：
Wright, G L Jr;Haley, C;Schellhammer, P F
前列腺特异性膜抗原（PSMA）是一种跨膜糖蛋白，可被鼠单克隆抗体（MAb）7 EII-C5.3以其天然形式（CYT-351）和免疫偶联物形式（CYT-356）识别。先前的研究表明，PSMA的组织表达高度限于前列腺组织。在这项研究中，进行了明确的免疫组织化学评价，以评估前列腺组织中的PSMA表达。通过将染色细胞的百分比乘以染色细胞的强度来建立染色指数，以提供各种组织类型中PSMA表达的定量测量。对PSMA的细胞定位、其与临床状态的相关性以及其与前列腺特异性抗原（PSA）表达的比较进行评价。前列腺特异性膜抗原被发现在大多数正常上皮内瘤变中高度表达，并且原发性和转移性前列腺肿瘤标本被评估。与PSA相反，PSMA表达通常是异质的，具有可变的染色模式，范围从正常前列腺上皮中的低水平弥漫性细胞质染色到高级别原发癌和转移组织中的非常强烈的细胞质和局灶性膜染色。由于MAb 7 EII-C5.3识别的PSMA跨膜糖蛋白的抗原表位位于胞质结构域，因此预期主要的胞质染色。良性前列腺肿瘤，即肥大，显示PSMA表达最低，染色指数为52，而正常前列腺和骨转移组织的染色指数分别为146和258。PSMA在良性前列腺组织中明显下调的原因尚不清楚，但可能与PSMA的剪接变体或翻译后修饰有关。PSMA的表达随着病理分级的增加而增加，但与临床分期无关。虽然PSMA在低分化和转移性前列腺肿瘤中过表达，但在原发性肿瘤中的表达与淋巴结状态、囊外浸润或精囊浸润无关。这些结果表明，PSMA不是疾病进展的有用生物标志物;然而，高表达似乎与更具侵袭性的前列腺癌表型相关。PSMA在转移性组织中的有限特异性、差异性前列腺组织表达和过表达支持继续研究这种独特的前列腺肿瘤相关生物标志物，以开发用于前列腺癌诊断和治疗的新策略。
Prostate-specific membrane antigen (PSMA) is a trans-membrane glycoprotein recognized by the murine monoclonal antibody (MAb) 7EII-C5.3 both in its native (CYT-351) and immunoconjugate form (CYT-356). Previous studies have shown that tissue expression of PSMA is highly restricted to prostate tissues. In this study, a definitive immunohistochemistry evaluation was performed to assess PSMA expression in prostate tissues. A stain index was established by multiplying the percentage of stained cells by the intensity of the stained cells to provide a quantitative measurement of PSMA expression in the various tissue types. The cellular location of PSMA, its correlation with clinical status, and its comparison with the expression of prostate-specific antigen (PSA) were evaluated. Prostate-specific membrane antigen was found to be highly expressed in most of the normal intraepithelial neoplasia, and the primary and metastatic prostate tumor specimens evaluated. In contrast to PSA, PSMA expression was often heterogeneous with variable staining patterns, ranging from a low-level diffuse cytoplasmic staining in normal prostate epithelium to very intense cytoplasmic and focal membrane staining in high-grade primary carcinomas and metastatic tissues. The predominant cytoplasmic staining was expected because the antigenic epitope of the PSMA transmembrane glycoprotein recognized by MAb 7EII-C5.3 is located in the cytoplasmic domain. Benign prostate tumors, ie, hypertrophy, showed the lowest expression of PSMA with a stain index of 52, compared with stain indexes of 146 and 258 for normal prostate and bone metastatic tissues, respectively. The reason for the apparent down-regulation of PSMA in benign prostate tissue is unknown but may be related to a splicing variant or post-translational modification of PSMA. Expression of PSMA was observed to increase with increasing pathologic grade, but not with clinical stage. Although PSMA was overexpressed in poorly differentiated and metastatic prostate tumors, expression in the primary tumor did not correlate with nodal status, extracapsular penetration, or seminal vesicle invasion. These results suggest that PSMA is not a useful biomarker of disease progression; however, high expression does appear to be associated with the more aggressive prostate carcinoma phenotype. The restricted specificity, differential prostate tissue expression, and overexpression of PSMA in metastatic tissues support the continued study of this unique prostate tumor-associated biomarker for developing new strategies for diagnostic and therapy of prostate cancer.