MYCN protein stability is a better prognostic indicator in neuroblastoma

Abstract

Objective MYCN oncogene amplification is associated with treatment failure and poor prognosis in neuroblastoma. To date, most detection methods of MYCN focus on DNA copy numbers instead of protein expression, which is the real one performing biological function, for poor antibodies. The current investigation was to explore a fast and reliable way to detect MYCN protein expression and evaluate its performance in predicting prognosis. Methods Several MYCN antibodies were used to detect MYCN protein expression by immunohistochemistry (IHC), and one was chosen for further study. We correlated the IHC results of MYCN from 53 patients with MYCN fluorescence in situ hybridization (FISH) and identified the sensitivity and specificity of IHC. The relationship between patient prognosis and MYCN protein expression was detected from this foundation. Results MYCN amplification status detected by FISH was most valuable for INSS stage 3 patients. In the cohort of 53 samples, IHC test demonstrated 80.0–85.7% concordance with FISH results. Further analyzing those cases with inconsistent results, we found that patients with MYCN amplification but low protein expression tumors always had a favorable prognosis. In contrast, if patients with MYCN non-amplified tumors were positive for MYCN protein, they had a poor prognosis. Conclusion MYCN protein level is better than MYCN amplification status in predicting the prognosis of neuroblastoma patients. Joint of FISH and IHC could confirm MYCN protein stability and achieve better prediction effect than the singular method.

Prominent Staining of MYCN Immunohistochemistry Predicts a Poor Prognosis in MYCN Non-Amplified Neuroblastoma

“…4 Moreover, MYCN non-amplified neuroblastomas still showed heterogeneity in disease progression. 16 Similar to previous reports, 8,19 MYCN protein expression was found in some MYCN non-amplified patients, who had an unfavorable outcome in our study. MYCN expression is not confined to tumors with MYCN gene amplification in neuroblastoma.…”

“…Our result was consistent with most of previous reports. 6,8,19,20 Moderate and strong staining may be considered as positive for MYCN IHC in day-to-day histopathology practice.…”

“…The combination of detecting of FISH and IHC was recommended in routine work, and its prediction effect may be better than the singular method. 8…”

“…6,7 However, there is no uniform MYCN immunohistochemistry (IHC) evaluation standard, and the results obtained from different studies are not completely consistent. 4,8 The aim of this study is to investigate the prognostic role of MYCN protein expression by IHC and compare the results of MYCN amplification and other clinical parameters in neuroblastoma.…”

Interplay: The Essential Role between INSM1 and N-Myc in Aggressive Neuroblastoma

“…The dysregulation of the N-Myc onco-protein plays a strong causative role in NB that induces widespread proliferation and inhibits the SA lineage cell apoptosis [ 43 , 44 , 45 ]. The molecular mechanisms of MYCN dysregulation are mostly driven by the disruption of transcription, translation, protein stability, apoptotic resistance, and metabolic flexibility [ 46 , 47 , 48 ].…”