ORIGINAL ARTICLES

Histological profile of tumours from MYCN transgenic mice

H C Moore¹, K M Wood², M S Jackson³, M A Lastowska³, D Hall³, H Imrie¹, C P F Redfern¹, P E Lovat¹, F Ponthan¹, K O’Toole¹, J Lunec¹ and D A Tweddle¹

¹ Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK
² Department of Cellular Pathology, Royal Victoria Infirmary, Newcastle upon Tyne, UK
³ Institute of Human Genetics, Newcastle University, Newcastle upon Tyne, UK

Correspondence to:
Dr D A Tweddle, Northern Institute for Cancer Research, Paul O’Gorman Building, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK; D.A.Tweddle{at}newcastle.ac.uk

Background: MYCN is the most commonly amplified gene in human neuroblastomas. This proto-oncogene has been overexpressed in a mouse model of the disease in order to explore the role of MYCN in this tumour.

Aims: To report the histopathological features of neuroblastomas from MYCN transgenic mice.

Methods: 27 neuroblastomas from hemizygous transgenic mice and four tumours from homozygous mice were examined histologically; Ki67 and MYCN immunocytochemistry was performed in 24 tumours.

Results: Tumours obtained from MYCN transgenic mice resembled human neuroblastomas, displaying many of the features associated with stroma-poor neuroblastoma, including heterogeneity of differentiation (but no overt ganglionic differentiation was seen), low levels of Schwannian stroma and a high mitosis karyorrhexis index. The tumours had a median Ki67 labelling index of 70%; all tumours expressed MYCN with a median labelling index of 68%. The most striking difference between the murine and human neuroblastomas was the presence of tingible body macrophages in the transgenic mouse tumours reflecting high levels of apoptosis. This has not previously been described in human or other murine neuroblastoma models.

Conclusions: These studies highlight the histological similarities between tumours from MYCN transgenic mice and human neuroblastomas, and reaffirm their role as a valuable model to study the biology of aggressive human neuroblastoma.

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