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Insulin Production in a Neuroectodermal Tumor that Expresses Islet Factor-1, But Not Pancreatic-Duodenal Homeobox 1

Department of Anatomy (T.N., M.F., S.A.) and Third Department of Medicine (A.K., H.K., Y.N., H.M., K.E., A.K., R.K.), Shiga University of Medical Science, Otsu, Shiga 520-2129, Japan; and Departments of Medicine and Biochemistry and Molecular Biology, University of Calgary Health Sciences Center (N.W.), Calgary, Alberta, Canada T2N 4N1

Address all correspondence and requests for reprints to: Dr. Atsunori Kashiwagi, Shiga University of Medical Science, Otsu, Shiga 520-2129, Japan. E-mail: kasiwagi{at}belle.shiga-med.ac.jp

We studied a 60-yr-old female with a brain tumor who showed severe symptoms of hypoglycemia (plasma glucose, 2.2 mmol/L) and hyperinsulinemia (1.28 nmol/L) after radiotherapy. The cystic brain tumor contained proinsulin and insulin at concentrations of 13.6 and 1.22 nmol/L, respectively. Immunohistochemical studies showed the tumor cells were ectodermal in origin but not endodermal, based on three diagnostic features of neuroectodermal tumors 1) pseudorosette formation noted under light microscopy, 2) finding of a small number of dense core neurosecretory granules on electron microscopy, and 3) positive immunostaining for both neuronal specific enolase and protein gene product 9.5. These cells also expressed the transcription factor, neurogenin-3, NeuroD/ß2, and islet factor I, which are believed to be transcription factors in neuroectoderm as well as in pancreatic islet cells, but not pancreatic-duodenal homeobox 1, Pax4, or Nkx2.2. In addition, they did not express glucagon, somatostatin, or glucagon-like peptide-1. Our results show the presence of proinsulin in an ectoderm cell brain tumor that does not express the homeobox gene, pancreatic-duodenal homeobox 1, but expresses other transcription factors, i.e. neurogenin3, NeuroD/ß2, and islet factor-1, which are related to insulin gene expression in the brain tumor.

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