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

作者：Wang L L; Teshiba R; Ikegaki N; Tang X X; Naranjo A; London W B; Hogarty M D; Gastier Foster J M; Look A T; Park J R; Maris J M; Cohn S L; Seeger R C; Asgharzadeh S; Shimada H^*

来源：British Journal of Cancer, 2015, 113(1): 57-63.

DOI：10.1038/bjc.2015.188

• neuroblastoma
• MYCN protein
• MYC protein
• immunohistochemistry
• prognosis

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(+), 38 (11%) were MYC(+), and one(0.3%) had both proteins(+). MYCN(+) tumours and MYC(+) tumours were more likely diagnosed in children > 18months with stage4-disease. MYCN(+) tumours were associated with amplified MYCN, Unfavourable Histology (UH), and High-MKI (Mitosis-Karyorrhexis Index). MYC(+) 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 = 167, 89.7 +/- 5.5% 3-year EFS, 97.0 +/- 3.2% 3-year OS), followed by UH patients without MYC/MYCN expressions (N = 84, 63.1 +/- 13.6% 3-year EFS, 83.5 +/- 9.4% 3-year OS). MYCN(+) patients and MYC(+) patients had similar and significantly low (P<0.0001) 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, similar to 30% 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.

• 出版日期2015-6-30