High expression of prostate-specific membrane antigen in the tumor-associated neo-vasculature is associated with worse prognosis in squamous cell carcinoma of the oral cavity
High expression of prostate-specific membrane antigen in the tumor-associated neo-vasculature is associated with worse prognosis in squamous cell carcinoma of the oral cavity
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DOI：
10.1038/modpathol.2012.66
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发表时间：
2012-08-01
期刊：
影响因子：
7.5
通讯作者：
Bander, Neil H.
中科院分区：
文献类型：
--
作者：
Haffner, Michael C.;Laimer, Johannes;Bander, Neil H.
前列腺特异性膜抗原 (PSMA) 是一种跨膜蛋白，在前列腺癌以及非前列腺实体瘤的新血管系统中表达。在这里，我们确定了口腔鳞状细胞癌脉管系统中 PSMA 的表达模式。使用先前验证的抗体，使用免疫组织化学方法对一组口腔鳞状细胞癌患者 (n = 96) 的 PSMA 染色分布和环氧合酶 2 (COX2) 表达状态进行评估，并将其与临床病理学特征和结果相关。 24 例 (25%) 病例未显示可检测到的 PSMA 染色，48 例 (50%) 病例在不到 50% 的微血管中显示出 PSMA 阳性免疫反应性，24 例 (25%) 病例在超过 50% 的肿瘤相关微血管中显示出强内皮 PSMA 表达。高内皮 PSMA 表达与生存期大幅缩短相关（18.2 个月 vs 77.3 个月；P - 0.0001），并且在多变量分析中调整级别和分期后仍保持预后意义（风险比 = 2.19，P = 0.007）。此外，我们观察到内皮 PSMA 与癌细胞特异性 COX2 表达之间存在很强的关联。总之，我们为口腔鳞状细胞癌中内皮 PSMA 表达的预后意义提供了第一个证据，并表明花生四烯酸代谢物与肿瘤新血管系统中内皮 PSMA 表达之间存在潜在的相互作用。现代病理学(2012) 25, 1079-1085; doi:10.1038/modpathol.2012.66； 2012 年 3 月 30 日在线发布
Prostate-specific membrane antigen (PSMA) is a transmembrane protein expressed in prostate cancer as well as in the neo-vasculature of nonprostatic solid tumors. Here, we determined the expression pattern of PSMA in the vasculature of oral squamous cell carcinoma. Using a previously validated antibody, PSMA staining distribution and cyclooxygenase 2 (COX2) expression status was evaluated in a cohort of patients with squamous cell carcinoma of the oral cavity (n = 96) using immunohistochemistry and was correlated with clinicopathological features as well as outcome. Twenty-four (25%) cases showed no detectable PSMA staining, 48 (50%) demonstrated positive immunoreactivity for PSMA in less than 50% of microvessels and 24 (25%) cases showed strong endothelial PSMA expression in more than 50% of tumor-associated microvessels. High endothelial PSMA expression was associated with greatly reduced survival (18.2 vs 77.3 months; P - 0.0001) and maintained prognostic significance after adjusting for grade and stage in multivariate analysis (hazard ratio = 2.19, P = 0.007). Furthermore, we observed a strong association between endothelial PSMA and cancer cell-specific COX2 expression. In conclusion, we provide the first evidence for the prognostic significance of endothelial PSMA expression in oral squamous cell carcinoma and, suggest a potential interaction between arachidonic acid metabolites and endothelial PSMA expression in the tumor neo-vasculature. Modern Pathology (2012) 25, 1079-1085; doi:10.1038/modpathol.2012.66; published online 30 March 2012