Augmented expression of MYC and/or MYCN protein defines highly aggressive MYC-driven neuroblastoma: a Children’s Oncology Group study

Background: MYCN amplification with subsequent MYCN protein overexpression is a powerful indicator of poor prognosis of neuroblastoma patients. Little is known regarding the prognostic significance of the homologous MYC protein expression in neuroblastoma. Methods: Immunostaining for MYCN and MYC protein was performed on 357 undifferentiated/poorly differentiated neuroblastomas. Results were analysed with other prognostic markers. Results: Sixty-seven (19%) tumours were MYCN( þ ), 38 (11%) were MYC( þ ), and one(0.3%) had both proteins( þ ). MYCN( þ ) tumours and MYC( þ ) tumours were more likely diagnosed in children418months with stage4-disease. MYCN( þ ) tumours were associated with amplified MYCN, Unfavourable Histology (UH), and High-MKI (Mitosis–Karyorrhexis Index). MYC( þ ) tumours were also frequently UH but not associated with MYCN amplification, and more likely to have low-/intermediate-MKI. Favourable Histology patients without MYC/MYCN expressions exhibited the best survival (N ¼ 167, 89.7±5.5% 3-year EFS, 97.0±3.2% 3-year OS), followed by UH patients without MYC/MYCN expressions (N ¼ 84, 63.1±13.6% 3-year EFS, 83.5±9.4% 3-year OS). MYCN( þ )patients and MYC( þ )patients had similar and significantly low (Po0.0001) survivals (46.2±12.0% 3-year EFS, 63.2±12.1% 3-year OS and 43.4±23.1% 3-year EFS, 63.5±19.2% 3-year OS, respectively). Notably, the prognostic impact imparted by MYC expression was independent from other markers. Conclusions: In this series, B30% of neuroblastomas had augmented MYCN or MYC expression with dismal survivals. Prospective study of MYC/MYCN protein expression signature as a new biomarker for high-risk neuroblastomas should be conducted.