Chan Elaine S, Pawel Bruce R, Corao Diana A, Venneti Sriram, Russo Pierre, Santi Mariarita, Sullivan Lisa M
Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Pediatr Dev Pathol. 2013 Jul-Aug;16(4):272-7. doi: 10.2350/12-06-1216-OA.1. Epub 2013 Mar 26.
Glypican-3 (GPC3) is a proteoglycan thought to play an important role during development. Germline GPC3 mutations are seen in the rare Simpson-Golabi-Behmel syndrome (SGBS), which predisposes patients to Wilms tumor, hepatoblastoma, and neuroblastoma. While numerous adult tumors have been evaluated by immunohistochemistry for GPC3, no comprehensive assessment has been done in pediatric tumors. We therefore investigated GPC3 expression in 143 pediatric central nervous system (CNS) tumors and 271 non-CNS tumors. Among non-CNS tumors, GPC3 expression was seen in 9/9 (100%) hepatoblastomas, 4/6 (67%) malignant rhabdoid tumors, 5/13 (38%) Wilms tumors, 11/37 (30%) alveolar rhabdomyosarcomas, and 8/45 (18%) embryonal rhabdomyosarcomas. All 136 neuroblastomas, 14 Ewing sarcoma/primitive neuroectodermal tumors, and 11 synovial sarcomas were immunonegative for GPC3. Among CNS tumors, GPC3 had restricted expression, with positivity in 6/6 (100%) atypical teratoid rhabdoid tumors and 1/4 (25%) craniopharyngiomas. The remaining 136 CNS tumors-23 medulloblastomas, 21 pilocytic astrocytomas, 13 gangliogliomas, 12 ependymomas, 12 glioblastomas, 11 choroid plexus neoplasms, 10 diffuse astrocytomas (grade II/III), 10 meningiomas, 8 dysembryoplastic neuroepithelial tumors, 8 oligodendrogliomas, 3 craniopharyngiomas, 3 germinomas, and 2 neurocytomas-were entirely negative for GPC3. These results showed GPC3 positivity in a number of non-CNS tumors, with no consistent discrimination between tumors that were or were not associated with SGBS. Within the CNS, GPC3 positivity was limited to a small subset of CNS neoplasms and may thus serve as a useful positive diagnostic biomarker (P < 0.0001) in addition to negative INI1/BAF47/SMARCB1 staining to differentiate atypical teratoid rhabdoid tumors from other high-grade pediatric brain tumors.
磷脂酰肌醇蛋白聚糖-3（GPC3）是一种蛋白聚糖，被认为在发育过程中发挥重要作用。在罕见的辛普森-戈拉比-贝梅尔综合征（SGBS）中可发现GPC3种系突变，该综合征使患者易患肾母细胞瘤、肝母细胞瘤和神经母细胞瘤。虽然已通过免疫组织化学对众多成人肿瘤进行了GPC3评估，但尚未对儿童肿瘤进行全面评估。因此，我们调查了143例儿童中枢神经系统（CNS）肿瘤和271例非CNS肿瘤中GPC3的表达情况。在非CNS肿瘤中，9/9（100%）肝母细胞瘤、4/6（67%）恶性横纹肌样瘤、5/13（38%）肾母细胞瘤、11/37（30%）肺泡横纹肌肉瘤和8/45（18%）胚胎性横纹肌肉瘤中可见GPC3表达。所有136例神经母细胞瘤、14例尤因肉瘤/原始神经外胚层肿瘤和11例滑膜肉瘤的GPC3免疫反应均为阴性。在CNS肿瘤中，GPC3表达受限，6/6（100%）非典型畸胎样横纹肌样瘤和1/4（25%）颅咽管瘤呈阳性。其余136例CNS肿瘤——23例髓母细胞瘤、21例毛细胞型星形细胞瘤、13例神经节胶质瘤、12例室管膜瘤、12例胶质母细胞瘤、11例脉络丛肿瘤、10例弥漫性星形细胞瘤（II/III级）、10例脑膜瘤、8例胚胎发育不良性神经上皮肿瘤、8例少突胶质细胞瘤、3例颅咽管瘤、3例生殖细胞瘤和2例神经细胞瘤——GPC3均为完全阴性。这些结果表明，许多非CNS肿瘤中GPC3呈阳性，在与SGBS相关或不相关的肿瘤之间没有一致的区分。在CNS内，GPC3阳性仅限于一小部分CNS肿瘤，因此除了INI1/BAF47/SMARCB1染色阴性外，GPC3还可作为一种有用的阳性诊断生物标志物（P<0.0
