Fujisawa Hironori, Marukawa Kohei, Hasegawa Mitsuhiro, Tohma Yasuo, Hayashi Yutaka, Uchiyama Naoyuki, Tachibana Osamu, Yamashita Junkoh
Department of Neurosurgery, Division of Neuroscience, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
J Neurosurg. 2002 Dec;97(6):1350-5. doi: 10.3171/jns.2002.97.6.1350.
Because of their histological similarities, it is occasionally difficult to differentiate neurocytoma and dysembryoplastic neuroepithelial tumor (DNT) from oligodendroglial tumors. This study was conducted to investigate genetic differences among these tumor types in terms of loss of heterozygosity on chromosomes 1p and 19q, and p53 gene mutation.
A total of 24 tumors were analyzed, consisting of eight central neurocytomas, three DNTs, seven oligodendrogliomas, four oligoastrocytomas, and two undetermined extraventricular tumors with neurocytoma features (ETNFs). Allelic loss was determined using microsatellite markers that cover the common deletions on chromosomes 1p and 19q in oligodendrogliomas. A p53 gene mutation was identified using polymerase chain reaction-single-strand conformation polymorphism analysis and subsequent direct sequencing. Immunohistochemical studies with synaptophysin and electron microscopy investigations were also conducted. Allelic loss on 1p and 19q was detected in six oligodendrogliomas (86%) and in three oligoastrocytomas (75%), but in none of the central neurocytomas or DNTs. A p53 missense mutation was detected at codon 161 (GCC-->ACC, Ala-->Thr) in only one oligoastrocytoma without allelic loss. Synaptophysin was expressed in all central neurocytomas and DNTs, in three oligodendrogliomas (43%), and in three oligoastrocytomas (75%). Of the ETNFs, one demonstrated synaptophysin expression and neural ultrastructures but lacked genetic alterations, whereas the other showed allelic loss on 1p and 19q but was negative immunohistochemically and ultrastructurally. The former was diagnosed as a potential intraparenchymal neurocytoma and the latter as an oligodendroglioma.
Despite histological similarities, central neurocytomas and DNTs are genetically distinct from oligodendroglial tumors. Examination for allelic loss on 1p and 19q and for p53 mutation can be useful for making this distinction.
由于神经细胞瘤、胚胎发育不良性神经上皮肿瘤(DNT)与少突胶质细胞瘤在组织学上存在相似性,偶尔难以区分。本研究旨在探讨这些肿瘤类型在1p和19号染色体杂合性缺失以及p53基因突变方面的遗传差异。
共分析了24例肿瘤,包括8例中枢神经细胞瘤、3例DNT、7例少突胶质细胞瘤、4例少突星形细胞瘤以及2例具有神经细胞瘤特征的未确定的脑室外肿瘤(ETNF)。使用覆盖少突胶质细胞瘤1p和19号染色体常见缺失区域的微卫星标记来确定等位基因缺失情况。通过聚合酶链反应-单链构象多态性分析及随后的直接测序来鉴定p53基因突变。还进行了突触素免疫组织化学研究和电子显微镜检查。在6例少突胶质细胞瘤(86%)和3例少突星形细胞瘤(75%)中检测到1p和19号染色体的等位基因缺失,但在中枢神经细胞瘤或DNT中均未检测到。仅在1例无等位基因缺失的少突星形细胞瘤中检测到p53错义突变,发生在密码子161(GCC→ACC,丙氨酸→苏氨酸)。所有中枢神经细胞瘤和DNT均表达突触素,3例少突胶质细胞瘤(43%)和3例少突星形细胞瘤(75%)表达突触素。在ETNF中,1例显示突触素表达和神经超微结构,但无基因改变,而另1例显示1p和19号染色体等位基因缺失,但免疫组织化学和超微结构检查均为阴性。前者被诊断为潜在脑实质内神经细胞瘤,后者被诊断为少突胶质细胞瘤。
尽管在组织学上存在相似性,但中枢神经细胞瘤和DNT在基因上与少突胶质细胞瘤不同。检测1p和19号染色体的等位基因缺失以及p53突变有助于进行这种区分。