Comparative Pathology of Nerve Sheath Tumors in Mouse Models and Humans

Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Cancer Research (Impact Factor: 9.33). 06/2004; 64(10):3718-24. DOI: 10.1158/0008-5472.CAN-03-4079
Source: PubMed


Despite the progress made in our understanding of the biology of neurofibromatosis (NF), the long-term clinical outcome for affected patients has not changed significantly in the past decades, and both NF1 and NF2 are still associated with a significant morbidity and a decreased life span. A number of NF1 and NF2 murine models have been generated to aid in the study of NF tumor biology and in the development of targeted therapies for NF patients. A single, universal pathological classification of the lesions generated in these murine models is essential for the validation of the models, for their analysis and comparison with other models, and for their future effective use in preclinical treatment trials. For the formulation of a pathological classification of these lesions, the WHO classification of human tumors was used as a reference. However, it was not adopted for the classification of the GEM lesions because of some important differences between the human and murine lesions. A novel classification scheme for peripheral nerve sheath tumors in murine models was therefore devised.

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    • "Tumors treated with each drug were histologically analyzed to determine tumor grade as previously described [43, 44]. Hematoxylin and eosin (H & E) staining was performed to assess cellularity and mitotic index, immunohistochemistry for S100β confirmed the Schwann cell origin of these tumors, and Ki67 immunohistochemistry demonstrated the level of cellular proliferation (Figure 3A). "
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    • "Histopathological and immunohistochemical (IHC) analyses of peripheral nervous system tissues taken from ΔPten/C-EGFR experimental animals demonstrated high-grade PNSTs compared with hyperplasia to low-grade PNSTs seen in Pten-het/C-EGFR animals by histology and Ki67 staining criteria as defined [20, 21] (Figures 3(a) and 3(b)). Mast cells were detected in these enlarged peripheral nerves by toluidine blue staining (data not shown). "
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