Schwechheimer K, Läufle R M, Schmahl W, Knödlseder M, Fischer H, Höfler H
Department of Neuropathology, University of Freiburg im Breisgau, Germany.
Hum Pathol. 1994 Aug;25(8):772-80. doi: 10.1016/0046-8177(94)90246-1.
The neu/c-erbB-2 oncogene encodes a 185 kd transmembrane protein (p185). Here we have used the monoclonal antibody (mAb) 3B5 to determine the expression of p185 in a series of fixed biopsy specimens of 180 human brain tumors, including the most frequent entities and, in addition, 18 recurrent gliomas with malignant progression. In summary, 3B5 immunoreaction was most prominent in astrocytomas of different grades of malignancies and in meningiomas. In World Health Organization (WHO) grade II astrocytomas mab 3B5-immunoreaction was related to the cytomorphological phenotype. Fibrillary astrocytomas showed no or only a weak immunoreaction (four of five, 80%) in contrast with protoplasmic or gemistocytic astrocytomas, where a strong reaction was observed in most cases (six of nine, 66.6%, and four of five, 80%, respectively). In WHO grade II to WHO grade IV astrocytomas a trend towards higher scores with increasing grade was found. In a limited number of cases (18 gliomas and two meningiomas) of the tumor series tested other mAbs against neu/c-erbB-2 epitopes, especially the mabs 9G6 and CB11, gave qualitatively comparable results. In WHO grade I pilocytic astrocytomas a wide range of 3B5 immunoreactivity has been observed. The results of in situ hybridization using a 32P-labeled neu/erbB-2 RNA probe performed on four WHO grade I and II astrocytomas, seven WHO grade IV glioblastomas, one WHO grade II oligoastrocytoma, one WHO grade III anaplastic astrocytoma, and three WHO grade I meningiomas were consistent with these immunomorphological data, and Northern blot analysis also indicated an overexpression of neu/c-erbB-2 mRNA in gliomas of different grades of malignancy and in meningiomas. These elevated neu-erbB-2 transcript levels occurred in the absence of gene amplification. In a second series of recurrent gliomas with malignant progression (n = 18) the higher 3B5-immunoreaction scores were apparent in the more malignant recurrent gliomas. In this series the overexpression of neu/c-erbB-2 parallels glioma progression. In our cases it was not, however, correlated with the postoperative relapse-free interval or with the overall length of survival.
neu/c-erbB-2癌基因编码一种185kd的跨膜蛋白（p185）。在此，我们使用单克隆抗体（mAb）3B5来测定p185在180例人脑肿瘤的一系列固定活检标本中的表达情况，这些标本包括最常见的肿瘤类型，此外还有18例发生恶性进展的复发性胶质瘤。总之，3B5免疫反应在不同恶性程度的星形细胞瘤和脑膜瘤中最为显著。在世界卫生组织（WHO）二级星形细胞瘤中，mAb 3B5免疫反应与细胞形态学表型相关。纤维型星形细胞瘤显示无或仅有微弱的免疫反应（5例中的4例，80%），与之形成对比的是原浆型或肥胖型星形细胞瘤，在大多数情况下观察到强烈反应（分别为9例中的6例，66.6%，以及5例中的4例，80%）。在WHO二级至WHO四级星形细胞瘤中，发现随着分级增加有得分升高的趋势。在测试的肿瘤系列中的少数病例（18例胶质瘤和2例脑膜瘤）中，针对neu/c-erbB-2表位的其他mAb，尤其是mAb 9G6和CB11，给出了定性上可比的结果。在WHO一级毛细胞型星形细胞瘤中观察到3B5免疫反应性的广泛范围。对4例WHO一级和二级星形细胞瘤、7例WHO四级胶质母细胞瘤、1例WHO二级少突星形细胞瘤、1例WHO三级间变性星形细胞瘤以及3例WHO一级脑膜瘤进行的使用32P标记的neu/erbB-2 RNA探针的原位杂交结果与这些免疫形态学数据一致，并且Northern印迹分析也表明neu/c-erbB-2 mRNA在不同恶性程度的胶质瘤和脑膜瘤中过表达。这些升高的neu-erbB-2转录水平在没有基因扩增的情况下出现。在第二组发生恶性进展的复发性胶质瘤（n = 18）中，在恶性程度更高的复发性胶质瘤中3B5免疫反应得分更高是明显的。在该组中，neu/c-erbB-2的过表达与胶质瘤进展平行。然而，在我们的病例中，它与术后无复发生存期或总生存期无关。
