Prostate-specific membrane antigen expression in the neovasculature of gastric and colorectal cancers
Prostate-specific membrane antigen expression in the neovasculature of gastric and colorectal cancers
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DOI：
10.1016/j.humpath.2009.06.003
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发表时间：
2009-12-01
期刊：
影响因子：
3.3
通讯作者：
Bander, Neil H.
中科院分区：
文献类型：
--
作者：
Haffner, Michael C.;Kronberger, Irmgard E.;Bander, Neil H.
前列腺特异性膜抗原（PSMA）是一种在前列腺癌细胞中高度过表达的II型跨膜金属肽酶，已被研究为前列腺癌的靶向分子。最近，还发现PSMA在多种非前列腺实体瘤的新生血管中表达。由于其独特的表达模式仅限于肿瘤相关的内皮细胞，PSMA也可能是一种有趣的血管靶向分子。本研究采用免疫组化法检测了119例原发性胃腺癌、130例原发性结直肠腺癌和24例结直肠腺癌转移灶中PSMA的表达。表达数据与临床病理信息相关。119例胃癌中79例（66%）和130例结直肠癌中110例（85%）的肿瘤相关新生血管中检测到PSMA表达。此外，19例肝转移瘤中16例（84%）和5例结直肠癌淋巴结转移瘤中4例（80%）的新生血管呈前列腺特异性膜抗原阳性。在结直肠癌中，高级别肿瘤有PSMA表达较高的趋势（斯皮尔曼r = 0.18，P = 0.046）。在胃癌或结直肠癌中未观察到PSMA表达与总生存期或无病生存期之间的相关性。这项研究首次深入研究了PSMA在胃癌和结直肠癌中的表达。由于其高度肿瘤限制性表达和其靶向治疗的可及性，PSMA代表了结直肠癌和胃癌中有希望的治疗和诊断靶点。(C)2009 Elsevier Inc. All rights reserved.
Prostate-specific membrane antigen (PSMA), a type II transmembrane metallo-peptidase highly overexpressed in prostate cancer cells, has been studied as a targeting molecule in prostate cancer. Recently, PSMA has also been found to be expressed in the neovasculature of multiple nonprostatic solid tumors. Because of its unique expression pattern limited to tumor-associated endothelial cells, PSMA may also be an interesting molecule for vascular targeting. In this study, PSMA expression was determined by immunohistochemistry in 119 cases of primary gastric adenocarcinoma, 130 cases of primary colorectal adenocarcinoma, and 24 metastasis of colorectal adenocarcinoma. Expression data were correlated with clinicopathologic information. PSMA expression was detected in tumor-associated neovasculature of 79 (66%) of 119 gastric and 110 (85%) of 130 colorectal carcinomas. Furthermore, the neovasculatures of 16 (84%) of 19 liver and 4 (80%) of 5 nodal metastases from colorectal carcinomas were prostate-specific membrane antigen positive. There was a trend for high-grade tumors to higher PSMA expression (Spearman r = 0.18, P = .046) in colorectal cancers. No association between PSMA expression and overall- or disease-free survival was observed in gastric or colorectal cancers. This study provides the first in-depth look at PSMA expression in gastric and colorectal cancer. Because of its highly tumor-restricted expression and its accessibility to targeted therapy, PSMA represents a promising therapeutic and diagnostic target in colorectal and gastric cancer. (C) 2009 Elsevier Inc. All rights reserved.