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. 2017 Mar 31:17:43.
doi: 10.1186/s12935-017-0412-z. eCollection 2017.

MYCN amplification predicts poor prognosis based on interphase fluorescence in situ hybridization analysis of bone marrow cells in bone marrow metastases of neuroblastoma

Zhi-Xia Yue  1 , Cheng Huang  1 , Chao Gao  1 , Tian-Yu Xing  1 , Shu-Guang Liu  1 , Xing-Jun Li  1 , Qian Zhao  1 , Xi-Si Wang  1 , Wen Zhao  1 , Mei Jin  1 , Xiao-Li Ma  1
Affiliations

MYCN amplification predicts poor prognosis based on interphase fluorescence in situ hybridization analysis of bone marrow cells in bone marrow metastases of neuroblastoma

Zhi-Xia Yue et al. Cancer Cell Int. .

Abstract

Background: MYCN gene amplification is related to risk stratification. Therefore it is important to identify accurately the level of the MYCN gene as early as possible in neuroblastoma (NB); however, for patients with bone marrow (BM) metastasis who need chemotherapy before surgery, timely detection of the MYCN gene is not possible due to the unavailability of primary tumors.

Methods: MYCN gene status was evaluated in 81 BM metastases of NB by interphase fluorescence in situ hybridization (FISH) analysis of BM cells. The clinicobiological characteristics and prognostic impact of MYCN amplification in NB metastatic to BM were analyzed.

Results: MYCN amplification was found in 16% of patients with metastases, and the results were consistent with the primary tumors detected by pathological tissue FISH. MYCN amplification was associated with age, lactate dehydrogenase (LDH) levels and prognosis (P = 0.038, P < 0.001, P = 0.026). Clinical outcome was poorer in patients with MYCN amplification than in those without amplification (3-year EFS 28.8 ± 13.1 vs. 69.7 ± 5.7%, P = 0.005; 3-year OS 41.5 ± 14.7 vs. 76.7 ± 5.5%, P = 0.005).

Conclusions: MYCN amplification predicts a poor outcome in NB metastatic to BM, and interphase FISH of bone marrow cells provides a timely direct and valid method to evaluate the MYCN gene status.

Keywords: Bone marrow metastasis; Fluorescence in situ hybridization; MYCN amplification; Neuroblastoma.

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Figures

Fig. 1
Fig. 1
Representative FISH images of BM cells. a The status of MYCN amplification using a dual-color probe. Green signals represent the specific probe for MYCN and red signals stand for centromeric chromosome 2 probes. MYCN signals show more than 30 copies within the nuclei. b The status of 1pLOH using a dual-color probe. Green signals represent the copy numbers at 1q21 and red signals are the specific DNA probe of 1p36. Bars 5 μm
Fig. 2
Fig. 2
The prognostic significance of MYCN amplification in bone marrow metastatic NB. a, b Event free survival (EFS) and overall survival (OS) of 81 patients stratified by MYCN status
See this image and copyright information in PMC

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