Loss of DCC expression and glioma progression.
Loss of DCC expression and glioma progression.
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发表时间：
1997-02
期刊：
影响因子：
11.2
通讯作者：
M. Reyes-Múgica;K. Rieger-Christ;H. Ohgaki;B. Ekstrand;M. Helie;G. Kleinman;A. Yahanda;E. Fearon;P. Kleihues;M. Reale
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作者：
M. Reyes-Múgica;K. Rieger-Christ;H. Ohgaki;B. Ekstrand;M. Helie;G. Kleinman;A. Yahanda;E. Fearon;P. Kleihues;M. Reale
大肠癌缺失基因（DCC）是染色体18 q21上的一个候选肿瘤抑制基因，编码神经细胞粘附分子家族蛋白，在神经系统中表达最高。为了解决DCC可能在胶质瘤发展和/或进展中发挥作用的假设，我们通过免疫组织化学方法检测了57例切除的人星形细胞肿瘤中DCC的表达。总体而言，低级别星形细胞瘤主要是DCC阳性（16例中的15例，或94%），而高级别肿瘤显着较少表达DCC蛋白（41例中的27例，或66%; P = 0.03）。我们能够直接评估DCC表达与15例患者的肿瘤进展之间的关系，这些患者最初表现为低级别星形细胞瘤，随后复发为胶质母细胞瘤。在来自同一患者的这组配对病变中，15例低度恶性肿瘤中有14例（93%）表达DCC蛋白，而15例相应的胶质母细胞瘤中只有7例（47%）为DCC阳性。我们还观察到，与原发性或新发胶质母细胞瘤（26例中6例，或23%; P = 0.05）相比，低级别星形细胞瘤恶性进展导致的继发性胶质母细胞瘤更常为DCC阴性（15例中8例，或53%）。这些发现暗示DCC失活在胶质瘤进展中，并且还表明DCC表达优先但不完全地在继发性多形性胶质母细胞瘤的遗传途径中丢失。
The deleted in colorectal cancer (DCC) gene, a candidate tumor suppressor gene on chromosome 18q21, encodes a neural cell adhesion molecule family protein that is most highly expressed in the nervous system. To address the hypothesis that DCC may play a role in glioma development and/or progression, we examined DCC expression by immunohistochemistry in 57 resected human astrocytic tumors. Overall, low-grade astrocytomas were predominantly DCC positive (15 of 16, or 94%), whereas high-grade tumors significantly less often expressed the DCC protein (27 of 41, or 66%; P = 0.03). We were able to directly assess the relationship between DCC expression and tumor progression in 15 patients who initially presented with a low-grade astrocytoma and subsequently recurred with a glioblastoma. Within this panel of paired lesions from the same patient, 14 of 15 (93%) low-grade tumors expressed the DCC protein, whereas only 7 of 15 (47%) corresponding glioblastomas were DCC positive. We also observed that secondary glioblastomas resulting from malignant progression of low-grade astrocytomas were more often DCC negative (8 of 15, or 53%) compared with primary or de novo glioblastomas (6 of 26, or 23%; P = 0.05). These findings implicate DCC inactivation in glioma progression and also demonstrate that DCC expression is preferentially, but not exclusively, lost in the genetic pathway to secondary glioblastoma multiforme.