Neurofibromin and NF1 gene analysis in composite pheochromocytoma and tumors associated with von Recklinghausen's disease

Mod Pathol. 2002 Mar;15(3):183-8. doi: 10.1038/modpathol.3880513.

Abstract

Composite tumor of pheochromocytoma and neuroblastoma, or ganglioneuroma, or ganglioneuroblastoma (composite pheochromocytoma), also known as mixed neuroendocrine and neural tumor, are sometimes combined with neurofibromatosis type 1 (NF1). To better understand the relationship between NF1 and composite pheochromocytoma, an immunohistochemical study using anti-neuro-fibromin that is an NF1 gene product and DNA sequence of NF1 Exon 31 were carried out in five cases of composite pheochromocytoma and in various tumors from five patients with NF1. Neurofibromin was not expressed in Schwann cells and sustentacular cells of composite pheochromocytomas and was very weakly or negatively expressed in neurofibroma of NF1 patients. However, it was strongly expressed in ganglionic cells and pheochromocytoma cells of the composite pheochromocytomas and also in mucosal ganglioneuromas, a gangliocytic paraganglioma, and in pheochromocytomas from the patients with NF1. Although there was no mutation in NF1 Exon 31, it could not be ruled out that there were mutations in other sites of the NF1 gene. Neurofibromin insufficiency may induce abnormal proliferation of Schwann cells in composite pheochromocytomas as well as in neurofibromatosis.

MeSH terms

  • Adrenal Gland Neoplasms / genetics*
  • Adrenal Gland Neoplasms / metabolism
  • Adrenal Gland Neoplasms / pathology
  • Adult
  • Aged
  • Base Sequence
  • Child
  • DNA Mutational Analysis
  • DNA, Neoplasm / analysis
  • Female
  • Genes, Neurofibromatosis 1*
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Neurofibromatosis 1 / genetics*
  • Neurofibromatosis 1 / metabolism
  • Neurofibromatosis 1 / pathology
  • Neurofibromin 1 / genetics*
  • Neurofibromin 1 / metabolism
  • Pheochromocytoma / genetics*
  • Pheochromocytoma / metabolism
  • Pheochromocytoma / pathology
  • Polymerase Chain Reaction
  • S100 Proteins / metabolism

Substances

  • DNA, Neoplasm
  • Neurofibromin 1
  • S100 Proteins