|Title:||MYCN RNA levels determined by quantitative in situ hybridization is better than MYCN gene dosages in predicting the prognosis of neuroblastoma patients||Authors:||HSIU-HAO CHANG
|Issue Date:||2020||Publisher:||Springer Nature||Journal Volume:||33||Journal Issue:||4||Start page/Pages:||531-540||Source:||Modern Pathology||Abstract:||
The aim of this study was to investigate the prognostic role of MYCN RNA expression by quantitative RNA in situ hybridization and its association with MYCN amplification in neuroblastoma. MYCN RNA expression in 69 neuroblastoma tumors was evaluated by an ultrasensitive quantitative RNA in situ hybridization technique, RNAscope. The correlations between MYCN RNA expression, MYCN amplification, and other clinicopathologic variables of neuroblastoma were analyzed. High expression levels of MYCN RNA were detected 30 of 69 (43%) of neuroblastomas, mainly in those with undifferentiated or poorly differentiated histology. High expression of MYCN RNA was significantly associated with MYCN amplification (P < 0.001) and other adversely prognostic factors, including older age at diagnosis (>18 months, P = 0.017), advanced clinical stage (International Neuroblastoma Staging System stage 3, 4, P = 0.002), unfavorable International Neuroblastoma Pathology Classification tumor histology (P < 0.001), and high-risk Children’s Oncology Group risk group (P = 0.001). In Kaplan–Meier analysis, MYCN RNA levels determined by quantitative in situ hybridization were better than MYCN gene dosages determined by chromogenic in situ hybridization in discriminating good and poor prognostic groups of neuroblastoma patients. In multivariate analysis, we further confirmed that high expression of MYCN RNA was an independent adverse prognostic factor for event-free and overall survival. Furthermore, high expression of MYCN RNA predicted unfavorable survival outcomes for neuroblastoma patients with MYCN non-amplification or high-risk Children’s Oncology Group risk group. In conclusion, our study is the first report to show the application of MYCN RNA in situ hybridization in neuroblastoma and established that high expression of MYCN RNA could be a better biomarker than MYCN amplification for predicting poor prognosis of neuroblastoma patients. ? 2019, The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.
|ISSN:||0893-3952||DOI:||10.1038/s41379-019-0410-x||SDG/Keyword:||messenger RNA; MYCN protein, human; N Myc proto oncogene protein; RNA; tumor marker; Article; autologous bone marrow transplantation; cancer chemotherapy; cancer patient; cancer prognosis; cancer radiotherapy; child; event free survival; female; gene amplification; gene dosage; high risk population; human; human tissue; in situ hybridization; infant; major clinical study; male; mRNA expression level; multimodality cancer therapy; MYCN gene; neuroblastoma; oncogene; overall survival; priority journal; real time reverse transcription polymerase chain reaction; comparative study; gene amplification; gene dosage; gene expression regulation; genetic predisposition; genetics; in situ hybridization; mortality; neuroblastoma; pathology; predictive value; preschool child; prognosis; real time polymerase chain reaction; retrospective study; reverse transcription polymerase chain reaction; Biomarkers, Tumor; Child; Child, Preschool; Female; Gene Amplification; Gene Dosage; Gene Expression Regulation, Neoplastic; Genetic Predisposition to Disease; Humans; In Situ Hybridization; Infant; Male; N-Myc Proto-Oncogene Protein; Neuroblastoma; Predictive Value of Tests; Prognosis; Real-Time Polymerase Chain Reaction; Retrospective Studies; Reverse Transcriptase Polymerase Chain Reaction; RNA, Neoplasm
|Appears in Collections:||醫學系|
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.