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MYCN protein stability is a better prognostic indicator in neuroblastoma
Yi Yang1, Jie Zhao2, Yingwen Zhang1
1Pediatric Translational Medicine Institute, Department of Hematology & Oncology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, National Health Committee Key Laboratory of Pediatric Hematology & Oncology, Shanghai, 200127, China.
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.
