Stage 4S Neuroblastoma: Molecular, Histologic, and Immunohistochemical Characteristics and Presence of 2 Distinct Patterns of MYCN Protein Overexpression-A Report From the Children's Oncology Group.
Stage 4S Neuroblastoma: Molecular, Histologic, and Immunohistochemical Characteristics and Presence of 2 Distinct Patterns of MYCN Protein Overexpression-A Report From the Children's Oncology Group.
复制标题
DOI：
10.1097/pas.0000000000001647
复制
发表时间：
2021-08-01
期刊：
影响因子：
--
通讯作者：
Shimada H
中科院分区：
文献类型：
--
作者：
Kawano A;Hazard FK;Chiu B;Naranjo A;LaBarre B;London WB;Hogarty MD;Cohn SL;Maris JM;Park JR;Gastier-Foster JM;Ikegaki N;Shimada H
4S期神经母细胞瘤(4SNB)与肿瘤的自发消退和良好的预后有关。然而，一小部分患者的预后很差。对儿童肿瘤组神经母细胞瘤病理参考实验室的185例神经母细胞瘤病例进行研究。FISH检测MYCN癌基因状态[非扩增(NA)与扩增(A)]，免疫组织化学检测MYC家族(MYCN/MYC)蛋白表达[无过表达(−)/(+/−)与过表达(+)]，国际神经母细胞瘤病理分类[组织学(FH)与不良组织学(UH)]评价患者的生存情况。MYCN-NA、FH、MYC家族蛋白(−)/(+/−)、NH(−)阳性14 7例(79.5%)，预后良好[5年无事件生存率(EFS)88.5±3.1%；5年总生存率(OS)94.1±2.3%]。在MYCN-NA肿瘤中，11例MYCN蛋白阳性，呈中等均匀(M/U)染色：FH(10/11)，NH(−)，1例同时表达MYC蛋白(+)，均存活。同时发现5例MYC蛋白(+)和5例MYCN(−)/(+/−)肿瘤，均为FH而无NH(4/5)，均存活。在MYCN-A肿瘤中，18例MYCN蛋白(+)呈强异质性(S/H)，9例UH(44.4±23.4%EFS/OS)，9例FH(68.6±19.2%EFS/OS)，15例NH(+)。2例MYCN-A阳性肿瘤均为FH和NH(−)/(+/−)，1例死亡。免疫组织化学检测MYCN蛋白过表达的S/H染色模式与MYCN扩增、NH(+)及预后不良有关。相反，M/U染色模式与MYCN无扩增和NH(−)相关，对4SNB患者没有不良预后影响。
Stage 4S neuroblastoma (4SNB) is associated with spontaneous tumor regression and an excellent prognosis. However, a small group of the patients have a poor prognosis. 185 4SNB cases filed at the Children’s Oncology Group Neuroblastoma Pathology Reference Laboratory were studied. MYCN oncogene status [Non-Amplified (NA) vs. Amplified (A)] determined by FISH, MYC-family (MYCN/MYC) protein expression [no-overexpression(−)/(+/−) vs. overexpression(+)] by immunohistochemistry and histopathology by International Neuroblastoma Pathology Classification [Favorable Histology (FH) vs. Unfavorable Histology (UH)] with particular attention to nucleolar hypertrophy [NH(−) vs. (+)] were assessed with patient survival. 147 (79.5%) tumors were MYCN-NA, FH, MYC-family protein(−)/(+/−), and NH(−) with a good prognosis [88.5+3.1% 5-year Event-free survival (EFS); 94.1+2.3% 5-year Overall survival (OS)]. Among MYCN-NA tumors, 11 demonstrated MYCN protein(+) with a moderate and uniform (M/U) staining pattern: they were FH(10/11), NH(−), one showed MYC protein(+) simultaneously, and all patients are alive. Also found were 5 MYC protein(+) and MYCN(−)/(+/−) tumors; they were FH without NH(4/5), and all patients are alive. Among MYCN-A tumors, 18 had MYCN protein(+) with a strong and heterogeneous (S/H) staining pattern, 9 had UH (44.4+23.4% EFS/OS) and 9 had FH (68.6+19.2% EFS/OS), and 15 showed NH(+). Two tumors had MYCN protein(−)/(+/−) despite MYCN-A; both were FH and NH(−), and one patient died. S/H staining pattern of MYCN protein overexpression by immunohistochemistry was associated with MYCN amplification, NH(+) and a poor prognosis. In contrast, the M/U staining pattern was associated with MYCN non-amplification and NH(−), and had no adverse prognostic effects for the 4SNB patients.