PMID- 22593502
OWN - NLM
STAT- MEDLINE
DCOM- 20120730
LR  - 20190402
IS  - 1791-7530 (Electronic)
IS  - 0250-7005 (Linking)
VI  - 32
IP  - 5
DP  - 2012 May
TI  - Vascular wall cells contribute to tumourigenesis in cutaneous neurofibromas of 
      patients with neurofibromatosis type 1. A comparative histological, 
      ultrastructural and immunohistochemical study.
PG  - 2139-58
AB  - Neurofibromas are benign nerve sheath tumours. They occur sporadically, singly or 
      few in number, and in neurofibromatosis type 1 (NF1), an autosomal inherited 
      disease. These tumours are composed of different cell types, e.g. nerve cells 
      (axons and axon sheaths), Schwann cells, mast cells, and fibroblasts. The local 
      control of tumour growth in NF1 is poorly understood. Identification of cell 
      markers could provide new information on the processes that are involved in 
      tumour growth. MATERIALS AND METHODS: NF1 patients were diagnosed according to 
      the revised NF1 diagnostic criteria proposed by the US National Institute of 
      Health. Fifteen cutaneous neurofibromas from eight patients (origin: trunk and 
      face) were excised, immediately immersion-fixed in Bouin's fixative and embedded 
      in paraffin. Six micrometre thin sections were incubated with a variety of 
      neuronal markers, connective tissue and glial cell markers, neurotrophic factors 
      and their receptors. In addition, material was fixed, embedded and further 
      processed for light and electron microscopic studies. RESULTS: The tumours were 
      composed of different cell types, e.g. nerve cells (axons and axon sheaths), 
      Schwann cells, mast cells, compartmentalising cells and fibroblasts. Neuronal 
      markers were identified in axons (neuron-specific protein gene product 9.5, 
      PGP9.5), in several cell types (neurofilament protein-200 kDa, NF-200) and glial 
      cells (protein S-100, S-100). In glial cells the immunoreactivity for fibroblast 
      surface protein (FSP) was scanty, low for cyclic 2,3-nucleotide 
      3'-phosphodiesterase (CNPase), strong for glucose transporter 1 (Glut-1) but 
      lacking for glial fibrillary acidic protein (GFAP). Schwann cells and so-called 
      compartmentalising cells exhibited immunoreactivity for neurotrophin receptor 
      protein TrkA (TrkA) and glial cell-derived neurotrophic factor (GDNF). GDNF 
      receptor alpha-1 (GFR-alpha1) exhibited distinct immunoreactivity in single axons, in 
      Schwann cells, and with lower intensity in some perineurial sheet cells. No 
      immunoreactivity was observed for the low-affinity neurotrophin receptor protein 
      p75(NTR), high-affinity receptor protein TrkB (TrkB), high-affinity receptor 
      protein TrkC (TrkC), the neurotrophin 3 (NT-3), and the brain-derived 
      neurotrophic factor (BDNF). CONCLUSION: Human cutaneous neurofibromas displayed a 
      pattern of neurotrophic factors and their receptor immunoreactivity, which is 
      characteristic of differentiated non-malignant tumours, and exhibited some 
      differences from that established in developing and differentiated control 
      Schwann cells (probably involved in the pathogenesis of the neurofibromas), as 
      well as tumour cells in the process of differentiation. Neurofibromas are highly 
      vascularized tumours and possess activated endothelial cells and pericytes. We 
      presume that most of the hyperplastic structural components of a neurofibroma are 
      generated from activated pericytes and smooth muscle cells of the small tumour 
      vessels which possess qualities of adult stem cells.
FAU - Friedrich, Reinhard E
AU  - Friedrich RE
AD  - Oral and Maxillofacial Surgery, Eppendorf University Hospital, University of 
      Hamburg, Martinistr. 52, D-20246 Hamburg, Germany. rfriedrich@uke.de
FAU - Holstein, Adolf-Friedrich
AU  - Holstein AF
FAU - Middendorff, Ralf
AU  - Middendorff R
FAU - Davidoff, Michail S
AU  - Davidoff MS
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Glucose Transporter Type 1)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Receptor, Nerve Growth Factor)
RN  - 0 (SLC2A1 protein, human)
RN  - 0 (UCHL1 protein, human)
RN  - EC 3.4.19.12 (Ubiquitin Thiolesterase)
SB  - IM
MH  - Brain-Derived Neurotrophic Factor/analysis
MH  - Glial Cell Line-Derived Neurotrophic Factor/analysis
MH  - Glial Fibrillary Acidic Protein/analysis
MH  - Glucose Transporter Type 1/analysis
MH  - Humans
MH  - Immunohistochemistry
MH  - Microscopy, Electron
MH  - Muscle, Smooth, Vascular/*pathology
MH  - Myocytes, Smooth Muscle/*pathology
MH  - Nerve Growth Factors/analysis
MH  - Neurofibroma/chemistry/*pathology/ultrastructure
MH  - Neurofibromatosis 1/*pathology
MH  - Receptor, Nerve Growth Factor/analysis
MH  - Skin Neoplasms/chemistry/*pathology/ultrastructure
MH  - Ubiquitin Thiolesterase/analysis
EDAT- 2012/05/18 06:00
MHDA- 2012/07/31 06:00
CRDT- 2012/05/18 06:00
PHST- 2012/05/18 06:00 [entrez]
PHST- 2012/05/18 06:00 [pubmed]
PHST- 2012/07/31 06:00 [medline]
AID - 32/5/2139 [pii]
PST - ppublish
SO  - Anticancer Res. 2012 May;32(5):2139-58.