Pinto Navin, Mayfield Jodi R, Raca Gordana, Applebaum Mark A, Chlenski Alexandre, Sukhanova Madina, Bagatell Rochelle, Irwin Meredith S, Little Anthony, Rawwas Jawhar, Gosiengfiao Yasmin, Delattre Olivier, Janoueix-Lerosey Isabelle, Lapouble Eve, Schleiermacher Gudrun, Cohn Susan L
Division of Pediatric Hematology/Oncology, Seattle Children's Hospital, Seattle, Washington.
Department of Pediatrics, University of New Mexico, Albuquerque, New Mexico.
Pediatr Blood Cancer. 2016 Jun;63(6):1019-23. doi: 10.1002/pbc.25934. Epub 2016 Feb 10.
Array comparative genomic hybridization (CGH) analyses of frozen tumors have shown strong associations between the pattern of chromosomal aberrations and outcome in patients with advanced-stage neuroblastoma. New platforms for analyzing chromosomal aberrations using formalin-fixed paraffin-embedded (FFPE) tissue have recently been developed. We sought to determine whether chromosomal microarray analysis (CMA) using FFPE tumors is feasible and if segmental chromosomal aberrations were prognostic of recurrence in localized neuroblastoma.
Patients with MYCN nonamplified International Neuroblastoma Staging System stage 1 and 2 disease who recurred were identified. CMA was performed with diagnostic FFPE samples using OncoScan™ FFPE Express 2.0. The prognostic significance of chromosomal pattern was validated in 105 patients with available CGH results.
In 26 evaluable patients, 11 recurred locally, nine had metastatic relapse, and six remained progression free >3 years from diagnosis. No chromosomal aberrations were identified in four tumors. Numerical chromosomal aberrations (NCAs) without segmental chromosomal aberration (SCA) were identified in 11 patients: six progressed locally, two had metastatic progression and 3 remained progression-free. Eleven patients had SCAs: four progressed locally, six developed metastatic progression and one remained progression-free. Five or more SCAs were only detected in tumors from patients who developed metastases (P = 0.0004). In the validation cohort, SCAs were associated with inferior event-free survival (EFS) compared to NCA (5-year EFS 68% ± 8.3% vs. 91% ± 3.6%, respectively; P = 0.0083).
It is feasible to evaluate chromosomal aberrations using FFPE neuroblastoma tissue. SCA is associated with inferior EFS in localized neuroblastoma patients, and multiple SCAs may be predictive of metastatic relapse.
对冷冻肿瘤进行的阵列比较基因组杂交（CGH）分析显示，晚期神经母细胞瘤患者的染色体畸变模式与预后之间存在密切关联。最近已开发出使用福尔马林固定石蜡包埋（FFPE）组织分析染色体畸变的新平台。我们试图确定使用FFPE肿瘤进行染色体微阵列分析（CMA）是否可行，以及节段性染色体畸变是否可预测局限性神经母细胞瘤的复发。
确定复发的MYCN未扩增的国际神经母细胞瘤分期系统1期和2期疾病患者。使用OncoScan™ FFPE Express 2.0对诊断性FFPE样本进行CMA。在105例有可用CGH结果的患者中验证染色体模式的预后意义。
在26例可评估患者中，11例局部复发，9例发生远处转移复发，6例自诊断后3年以上无进展。4个肿瘤未发现染色体畸变。11例患者发现无节段性染色体畸变（SCA）的数值染色体畸变（NCA）：6例局部进展，2例发生远处转移进展，3例无进展。11例患者有SCA：4例局部进展，6例发生远处转移进展，1例无进展。仅在发生转移的患者的肿瘤中检测到5个或更多SCA（P = 0.0004）。在验证队列中，与NCA相比，SCA与无事件生存期（EFS）较差相关（5年EFS分别为68%±8.3%和91%±3.6%；P = 0.0083）。
使用FFPE神经母细胞瘤组织评估染色体畸变是可行的。SCA与局限性神经母细胞瘤患者的EFS较差相关，多个SCA可能预测远处转移复发。
