Brown H G, Kepner J L, Perlman E J, Friedman H S, Strother D R, Duffner P K, Kun L E, Goldthwaite P T, Burger P C
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
J Neuropathol Exp Neurol. 2000 Oct;59(10):857-65. doi: 10.1093/jnen/59.10.857.
495 medulloblastomas (MBs) from 6 Pediatric Oncology Group (POG) protocols were reviewed to assess the incidence and prognostic significance of "large cell" and "anaplastic" variants. "Large cell" medulloblastomas (LC MBs) were those with focal or diffuse, large, round neoplastic cells with prominent nucleoli. "Anaplastic" MBs (A MBs) were those with nuclei that were also large but markedly atypical with coarse chromatin and irregular shapes. Twenty-one cases were identified in the combined LC/A MB group, comprising about 4% of all MBs. Survival curves and Kaplan-Meier estimates of survival probabilities were examined separately for the LC/A MB and control groups. The logrank test for detecting poorer survival in the 21 cases was significant (p < 0.0001). Fluorescence in situ hybridization for c-myc showed amplification in 4 of 11 cases of the LC/A phenotype and 1 additional case of high level gain at 8q24 was disclosed by comparative genomic hybridization. Comparative genomic hybridization confirmed c-myc amplification and found evidence for isochromosome 17q in 3 of 4 LC/A cases studied successfully. One additional tumor showed high level gain restricted to 2p13 consistent with n-myc amplification. Monosomy 22, common in atypical teratoid/rhabdoid tumors, was not found. These results suggest that LC/A MB phenotype could be, at least in part, a correlate of c-myc, and possibly n-myc, amplification. The study thus confirms original observations about the LC MB in regard to histological features, immunohistochemical findings, c-myc amplification, cytogenetic findings, and poor prognosis.
对来自6个儿科肿瘤学组（POG）方案的495例髓母细胞瘤（MBs）进行了回顾，以评估“大细胞”和“间变性”变体的发生率及预后意义。“大细胞”髓母细胞瘤（LC MBs）是指具有局灶性或弥漫性、大的圆形肿瘤细胞且核仁突出的肿瘤。“间变性”MBs（A MBs）是指细胞核也大但明显异型，染色质粗糙且形状不规则的肿瘤。在LC/A MB联合组中识别出21例，约占所有MBs的4%。分别对LC/A MB组和对照组检查生存曲线及Kaplan-Meier生存概率估计值。检测这21例患者较差生存情况的对数秩检验具有显著性（p < 0.0001）。c-myc的荧光原位杂交显示，11例LC/A表型病例中有4例出现扩增，比较基因组杂交还发现另外1例8q24高水平获得。比较基因组杂交证实了c-myc扩增，并在成功研究的4例LC/A病例中的3例发现了17号染色体等臂体的证据。另外1例肿瘤显示高水平获得局限于2p13，与n-myc扩增一致。未发现非典型畸胎样/横纹肌样肿瘤中常见的22号染色体单体。这些结果表明，LC/A MB表型至少部分可能与c-myc以及可能的n-myc扩增相关。该研究因此证实了关于LC MB在组织学特征、免疫组化结果、c-myc扩增、细胞遗传学结果及预后不良方面的原始观察结果。
