Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
Neurol India. 2009 Sep-Oct;57(5):559-66. doi: 10.4103/0028-3886.57795.
Due to overlapping histomorphological features, difference in clinical behavior and treatment response, establishing potential molecular markers to facilitate diagnosis of various genetic subtypes of diffuse gliomas is essential.
To analyze 1p/19q status in diffuse gliomas and correlate it with epidermal growth factor receptor (EGFR) and p53 protein expression.
1p/19q status in 43 cases was evaluated by fluorescence in situ hybridization assay. Glial fibrillary acidic protein (GFAP), EGFR and p53 were assessed by immunohistochemistry.
Glial fibrillary acidic protein immunopositivity was observed in oligodendrogliomas within minigemistocytes and gliofibrillary oligodendrocytes as perinuclear homogenous blobs. It also highlighted the intermingled reactive astrocytes. Astrocytomas and the astrocytic component of oligoastrocytomas showed a diffuse fibrillary type of staining. 1p and/or 19q loss was seen in 65% (13/20) of oligodendrogliomas and 66.6% (5/9) of mixed oligoastrocytomas. There was one case each of pediatric oligodendroglioma and mixed oligoastrocytoma, none of which showed 1p/19q loss. None of the astrocytomas including two pediatric cases showed this alteration (P < 0.05). p53 was expressed in 57.1% of astrocytomas (8/14), 33% of mixed oligoastrocytomas (3/9) and 10% of oligodendrogliomas (2/20). Majority of oligodendrogliomas (85%; 17/20) and oligodendroglial areas in mixed oligoastrocytomas (77.7%; 7/9) showed a membranous lace-like immunopositivity with EGFR. In contrast, all astrocytomas (Grade II and III) were EGFR negative.
Loss of 1p/19q is strongly associated with oligodendroglial phenotype, while astrocytic tumors are more likely to show p53 over-expression. p53 expression and 1p/19q status appear to be mutually exclusive.
由于重叠的组织形态学特征、临床行为和治疗反应的差异,确定有助于诊断各种弥漫性神经胶质瘤遗传亚型的潜在分子标志物是至关重要的。
分析弥漫性神经胶质瘤中 1p/19q 状态,并与表皮生长因子受体(EGFR)和 p53 蛋白表达相关联。
通过荧光原位杂交检测 43 例患者的 1p/19q 状态。通过免疫组织化学评估神经胶质纤维酸性蛋白(GFAP)、EGFR 和 p53 的表达。
少突胶质细胞瘤中的小胶质细胞和神经胶质纤维性少突胶质细胞内可见神经胶质纤维酸性蛋白免疫阳性,表现为核周均匀块状。它还突出了混杂的反应性星形细胞。星形细胞瘤和少突星形细胞瘤的星形细胞成分显示弥漫性纤维状染色。1p 和/或 19q 缺失见于 65%(13/20)的少突胶质细胞瘤和 66.6%(5/9)的混合性少突星形细胞瘤。有一例儿童少突胶质细胞瘤和一例混合性少突星形细胞瘤,均未见 1p/19q 缺失。无一例星形细胞瘤,包括两例儿童病例,显示这种改变(P<0.05)。p53 在 57.1%的星形细胞瘤(8/14)、33%的混合性少突星形细胞瘤(3/9)和 10%的少突胶质细胞瘤(2/20)中表达。大多数少突胶质细胞瘤(85%;17/20)和混合性少突星形细胞瘤中的少突胶质细胞区(77.7%;7/9)显示 EGFR 膜状花边样免疫阳性。相比之下,所有星形细胞瘤(Ⅱ级和Ⅲ级)均为 EGFR 阴性。
1p/19q 的缺失与少突胶质细胞表型密切相关,而星形细胞瘤更可能表现出 p53 过度表达。p53 表达和 1p/19q 状态似乎是相互排斥的。