<p class="first" id="d6306608e180">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.
</p>