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Br J Cancer. 2015 Jun 30;113(1):57-63. doi: 10.1038/bjc.2015.188. Epub 2015 Jun 2.

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

Author information

1
Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA 90027, USA.
2
Department of Anatomy and Cell Biology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.
3
Department of Biostatistics, Children's Oncology Group Statistics and Data Center, University of Florida, Gainesville, FL 32607, USA.
4
Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
5
Division of Oncology and Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
6
Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital and Departments of Pathology and Pediatrics, Ohio State University College of Medicine, Columbus, OH 43210, USA.
7
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
8
Department of Pediatrics, Seattle Children's Hospital, University of Washington School of Medicine and Fred Hutchinson Cancer Research Center, Seattle, WA 98105, USA.
9
Department of Pediatrics, Division of Hematology/Oncology, University of Chicago, Chicago, IL 60637, USA.
10
Division of Hematology/Oncology, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA 90027, USA.

Abstract

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, ∼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.

PMID:
26035700
PMCID:
PMC4647535
DOI:
10.1038/bjc.2015.188
[Indexed for MEDLINE]
Free PMC Article

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