Identification of Subsets of Neuroblastomas by Combined Histopathologic and N-myc Analysis

Shimada, Hiroyuki; Stram, Daniel O.; Chatten, Jane; Joshi, Vijay V.; Hachitanda, Yoichi; Brodeur, Garrett M.; Lukens, John N.; Matthay, Katherine K.; Seeger, Robert C.

doi:10.1093/jnci/87.19.1470

Cited by 148 publications

(96 citation statements)

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“…In conclusion, the present findings confirm previous reports indicating that MKI is in NTs a reliable morphological marker of clinical behaviour and identifies favourable and unfavourable NTs (Shimada et al, 1995(Shimada et al, , 1999b(Shimada et al, , 2001Ambros et al, 2002). Our results also show that karyorrhectic cells represent the end-stage of a cascade of events leading to morphologically recognisable apoptosis, although none of these individual events is able by itself to determine the clinical relevance of the entire apoptotic process.…”

Section: Discussionsupporting

confidence: 91%

“…Our results show that a high MKI is associated with advanced stage, NB histological category, MYCN amplification and poor outcome, thus confirming previous findings reported by Shimada et al (1995Shimada et al ( , 1999bShimada et al ( , 2001) and Ambros et al (2002). However, when the levels of expression of key genes involved in apoptosis were compared to either MKI and clinicobiological features, no significant associations were found.…”

Section: Discussionsupporting

confidence: 90%

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Morphological and molecular assessment of apoptotic mechanisms in peripheral neuroblastic tumours

et al. 2006

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Multiple defects in apoptotic pathways have been described in peripheral neuroblastic tumours (NTs). Mitosis -karyorrhexis index (MKI) is a reliable morphological marker identifying favourable and unfavourable NTs. The extent to which apoptotic processes contribute to determine the clinical significance of MKI is still undefined. Apoptosis was investigated in a series of 110 peripheral NTs by comparing MKI to immunohistochemical and molecular apoptotic features. High MKI was found in 55 out of 110 NTs (50%) and was associated with advanced stage (P ¼ 0.007), neuroblastoma (NB) histological category (P ¼ 0.024), MYCN amplification (Po0.001), and poor outcome (P ¼ 0.011). Overall survival probability was 45% in patients with high MKI compared to 73% in patients with low MKI. In the same 110 NTs, the expression of Bcl-2, Bcl-X L , Bax and Mcl-1 was studied by immunohistochemistry, but no significant associations were found with clinicohistological features. Microarray analysis of apoptotic genes was performed in 40 out of 110 representative tumours. No significant association was found between the expression of apoptotic genes and MKI or clinicohistological features. Proliferative activity was assessed in 60 out of 110 representative tumours using Ki67 immunostaining, but no significant correlations with MKI or clinicobiological features were found. In NTs, the combination of apoptosis and proliferation as expressed by MKI is a significant prognostic parameter, although neither of them is per se indicative of the clinicobiological behaviour and outcome.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 90%

Morphological and molecular assessment of apoptotic mechanisms in peripheral neuroblastic tumours

et al. 2006

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“…The preparations were further incubated with pan-neurofilament monoclonal antibody (DPC, Los Angeles, CA). The preparations were then washed and placed into solution containing antimouse antibodies conjugated with CyDye (Cy3, Amersham, Buchs, UK) or FITC-conjugated goat F(abЈ) 2 antimouse immunoglobulin (Ig) (Janssen, Baerse, Belgium). The stained cells were examined with the aid of a Zeiss Axioscope fluorescence microscope (Carl Zeiss).…”

Section: Immunofluorescencementioning

confidence: 99%

Interferon-? cooperates with retinoic acid and phorbol ester to induce differentiation and growth inhibition of human neuroblastoma cells

et al. 2001

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The prognosis of patients with advanced stages of neuroblastoma with N-myc amplification remains poor despite escalated therapy, a situation that has called for alternative therapeutic approaches. Neuroblastoma cells, which represent immature peripheral neuronal cells, treated with certain physiologic and nonphysiologic agents such as retinoic acid (RA), phorbol esters and interferons (IFN) in vitro undergo cellular differentiation and stop to divide, a process that mimics normal neuronal development. Such "differentiation therapy" using RA after autologous bone marrow transplantation has recently given encouraging results in neuroblastoma patients with advanced disease. Considering approaches for improved differentiation therapy, we investi-

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“…The majority of the primary tumor cells stained positively for MYCN (Fig. 2) and the formation of nests or lobules surrounded by thin fibrovascular septa was observed, which are characteristics of human neuroblastomas with MYCN amplification (29). Next, the proliferation status of primary neuroblastoma tumors from TH-MYCN mice was investigated.…”

Section: Primary Neuroblastoma Tumors Are Composed Predominantly Of Pmentioning

confidence: 99%

Phox2B correlates with MYCN and is a prognostic marker for neuroblastoma development

Zhang

Zhao

et al. 2015

Oncology Letters

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Abstract. Neuroblastoma is the one of the most common extracranial childhood malignancies, accounting for ~15% of tumor-associated deaths in children. It is generally considered that neuroblastoma originates from neural crest cells in the paravertebral sympathetic ganglia and the adrenal medulla. However, the mechanism by which neuroblastoma arises during sympathetic neurogenesis and the cellular mechanism that drives neuroblastoma development remains unclear. The present study investigated the cell components during neuroblastoma development in the tyrosine hydroxylase-v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (TH-MYCN) mouse model, a transgenic mouse model of human neuroblastoma. The present study demonstrates that paired-like homeobox 2b (Phox2B) + neuronal progenitors are the major cellular population in hyperplastic lesions and primary tumors. In addition, Phox2B + neuronal progenitors in hyperplastic lesions or primary tumors were observed to be in an actively proliferative and undifferentiated state. The current study also demonstrated that high expression levels of Phox2B promotes neuroblastoma cell proliferation and xenograft tumor growth. These findings indicate that the proliferation of undifferentiated Phox2B + neuronal progenitors is a cellular mechanism that promotes neuroblastoma development and indicates that Phox2B is a critical regulator in neuroblastoma pathogenesis.

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Identification of Subsets of Neuroblastomas by Combined Histopathologic and N-myc Analysis

Abstract: Neuroblastomas with N-myc amplification have a characteristic histopathologic phenotype and an aggressive clinical course. In contrast, neuroblastomas without N-myc amplification exhibit a wide range of histologic features that can define prognostic subsets.

Cited by 148 publications

References 0 publications

Morphological and molecular assessment of apoptotic mechanisms in peripheral neuroblastic tumours

Morphological and molecular assessment of apoptotic mechanisms in peripheral neuroblastic tumours

Interferon-? cooperates with retinoic acid and phorbol ester to induce differentiation and growth inhibition of human neuroblastoma cells

Phox2B correlates with MYCN and is a prognostic marker for neuroblastoma development

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