Schulz S, Pauli S U, Schulz S, Händel M, Dietzmann K, Firsching R, Höllt V
Department of Pharmacology and Toxicology, Otto-von-Guericke-University, Magdeburg, Germany.
Clin Cancer Res. 2000 May;6(5):1865-74.
Meningioma is one of a variety of human tumors that exhibit a very high density of somatostatin receptors and in many cases show a true positive somatostatin receptor scintigraphy. However, the level of expression of individual somatostatin receptor proteins in meningioma has not been investigated. We have recently developed a panel of somatostatin receptor subtype-specific antibodies that effectively stain formalin-fixed, paraffin-embedded tumor tissue (S. Schulz et al., Clin. Cancer Res., 4: 2047-2052, 1998). In the present study, we have used these antibodies to determine the somatostatin receptor status of 40 randomly selected meningiomas. Immunoreactive staining for all somatostatin receptors was clearly located at the plasma membrane of the tumor cells and completely blocked with antigenic peptide. The vast majority of tumors (29 cases; 70%) were positive for sst2A immunoreactivity; among these, 20 (69%) tumors showed high levels of sst2A immunoreactivity. In contrast, all other somatostatin receptors were only detected sporadically, and none of these cases revealed a particularly strong staining. However, it is uncertain to what extent somatostatin receptor-immunoreactive staining intensity may translate into somatostatin receptor protein expression on the tumor cells. Therefore, in a prospective study, 16 surgically removed meningiomas were collected, and the level of sst2A expression was determined using Western blot analysis. Whereas sst2A was readily detectable as a broad band migrating at Mr 70,000 in 12 (75%) of these tumors, 8 tumors (50%) showed particularly high levels of immunoreactive sst2A receptors. There was an excellent correlation (P < 0.001) between the level of sst2A protein expression detected in Western blots and the sst2A- immunoreactive staining seen in tissue sections. Thus, the frequent overexpression of the sst2A receptor may explain the high tracer uptake often observed in meningioma patients during somatostatin receptor scintigraphy. Moreover, this simple immunohistochemical method could prove useful in identifying those cases of recurrent disease that may possibly respond to therapy with sst2-selective agonists.
脑膜瘤是多种人类肿瘤之一，其生长抑素受体密度非常高，并且在许多情况下表现出真正的生长抑素受体闪烁显像阳性。然而，脑膜瘤中各个生长抑素受体蛋白的表达水平尚未得到研究。我们最近开发了一组生长抑素受体亚型特异性抗体，这些抗体能有效地对福尔马林固定、石蜡包埋的肿瘤组织进行染色（S. Schulz等人，《临床癌症研究》，4: 2047 - 2052，1998）。在本研究中，我们使用这些抗体来确定40例随机选取的脑膜瘤的生长抑素受体状态。所有生长抑素受体的免疫反应性染色明显位于肿瘤细胞的质膜上，并且被抗原肽完全阻断。绝大多数肿瘤（29例；70%）对sst2A免疫反应呈阳性；其中，20例（69%）肿瘤显示出高水平的sst2A免疫反应性。相比之下，所有其他生长抑素受体只是偶尔被检测到，并且这些病例中没有一个显示出特别强烈的染色。然而，生长抑素受体免疫反应性染色强度在多大程度上能转化为肿瘤细胞上的生长抑素受体蛋白表达尚不确定。因此，在一项前瞻性研究中，收集了16例手术切除的脑膜瘤，并使用蛋白质印迹分析来确定sst2A的表达水平。在这些肿瘤中的12例（75%）中，sst2A很容易被检测到，表现为在Mr 70,000处迁移的一条宽带，8例肿瘤（50%）显示出特别高水平的免疫反应性sst2A受体。蛋白质印迹中检测到的sst2A蛋白表达水平与组织切片中看到的sst2A免疫反应性染色之间存在极好的相关性（P < 0.001）。因此，sst2A受体的频繁过度表达可能解释了在生长抑素受体闪烁显像期间脑膜瘤患者中经常观察到的高示踪剂摄取。此外，这种简单的免疫组织化学方法可能有助于识别那些可能对sst2选择性激动剂治疗有反应的复发病例。
