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

ABSTRACT: 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.Immunostaining for MYCN and MYC protein was performed on 357 undifferentiated/poorly differentiated neuroblastomas. Results were analysed with other prognostic markers.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.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.

SUBMITTER: Wang LL

PROVIDER: S-EPMC4647535 | biostudies-other | 2015 Jun

REPOSITORIES: biostudies-other

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

Wang L L LL Teshiba R R Ikegaki N N Tang X X XX Naranjo A A London W B WB Hogarty M D MD Gastier-Foster J M JM Look A T AT Park J R JR Maris J M JM Cohn S L SL Seeger R C RC Asgharzadeh S S Shimada H H

British journal of cancer 20150602 1

<h4>Background</h4>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.<h4>Methods</h4>Immunostaining for MYCN and MYC protein was performed on 357 undifferentiated/poorly differentiated neuroblastomas. Results were analysed with other prognostic markers.<h4>Results</h4>Sixty-seven (19%) tumours were MYCN(+ ...[more]

PMID: 26035700

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Project description:Dedifferentiated/undifferentiated endometrial carcinoma (DDEC/UEC) is an endometrial cancer characterized by the presence of histologically undifferentiated carcinoma. Genomic inactivation of core switch/sucrose nonfermentable (SWI/SNF) complex proteins was recently identified in approximately two-thirds of DDEC/UEC. The aim of this study was to delineate the clinical behavior of SWI/SNF-deficient DDEC/UEC in comparison to SWI/SNF-intact DDEC/UEC. The study cohort consisted of 56 SWI/SNF-deficient DDEC/UEC (2 POLE-mutated), which showed either SMARCA4 (BRG1) loss, ARID1A/1B co-loss, or SMARCB1 (INI1) loss in the undifferentiated tumor, and 26 SWI/SNF-intact DDEC/UEC (4 POLE-mutated). The average age at diagnosis was 61 years for patients with SWI/SNF-deficient tumors and 64 years for SWI/SNF-intact tumors. Mismatch repair (MMR) protein deficiency was seen in 66% of SWI/SNF-deficient and 50% of SWI/SNF-intact tumors. At initial presentation, 55% of patients with SWI/SNF-deficient tumors had extrauterine disease spread in contrast to 38% of patients with SWI/SNF-intact tumors. The 2-year disease specific survival (DSS) for stages I and II disease was 65% for SWI/SNF deficient tumors relative to 100% for SWI/SNF-intact tumors (p = 0.042). For patients with stages III and IV disease, the median survival was 4 months for SWI/SNF-deficient tumors compared to 36 months for SWI/SNF-intact tumors (p = 0.0003). All six patients with POLE-mutated tumors, including one with stage IV SWI/SNF-deficient tumor were alive with no evidence of disease. Among the patients with advanced stage SWI/SNF-deficient tumors, 68% (21 of 31) received adjuvant or neoadjuvant chemotherapy (platinum/taxane-based) and all except the patient with a POLE-mutated tumor (20 of 21) experienced disease progression either during chemotherapy or within 4 months after its completion. These findings show that core SWI/SNF-deficiency defines a highly aggressive group of undifferentiated cancer characterized by rapid disease progression that is refractory to conventional platinum/taxane-based chemotherapy. This underscores the importance of accurate clinical recognition of this aggressive tumor and the need to consider alternative systemic therapy for these tumors.

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

Publications

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

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