Abstract
Approximately one third of the female mice of the LTXBO strain develop spontaneous ovarian teratomas. These tumors contain a large neuroepithelial component, which includes primitive neural structures resembling embryonic neural tubes (medulloepithelial rosettes), ependymoblastic and ependymal rosettes, neuroblasts, mature ganglionic neurons, myelinated neurites, and astrocytes. The purpose of this study was to characterize these tumors according to the immunohistochemical location of some well-characterized trophic and regulatory neuropeptides and neurotransmitters, several neuronal-associated cytoskeletal proteins, and other proteins indicative of neuronal and glial differentiation. Medulloepithelial rosettes showed focal serotonin-like, opioid peptide-like and gamma-amino butyric acid-like immunoreactivity, and displayed immunostaining for the neuron-associated class III beta-tubulin isotype. The mature ganglion cells were also immunoreactive for these markers, and, in addition, for somatostatin, cholecystokinin, bombesin, glucagon, vasoactive intestinal peptide, and neuropeptide Y. Mature ganglion cells were also immunoreactive for proteins associated with the neuronal cytoskeleton (including microtubule-associated proteins, MAP2 and tau, and higher molecular weight phosphorylated and non-phosphorylated neurofilament subunits), neuron-specific enolase, and synaptophysin. Undifferentiated stem cells, ependymoblastic and ependymal rosettes, and astroglia all stained with a monoclonal antibody that recognizes all mammalian beta-tubulin isotypes, but did not react with antibodies to neuronal-associated cytoskeletal proteins or neuropeptides. Neuropeptide-like immunoreactivity and demonstration of the class III beta-tubulin isotype indicate early neuronal commitment in neoplastic primitive neuroepithelium. These patterns of immunoreactivity closely follow those encountered in the normal neurocytogenesis of the mammalian and avian forebrain, and increase the precision with which the early stages of progressive neuroepithelial differentiation can be analyzed in human embryonal tumors of the CNS.
Full text
PDF












Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Andrews P. W. Human teratocarcinomas. Biochim Biophys Acta. 1988 Aug 3;948(1):17–36. doi: 10.1016/0304-419x(88)90003-0. [DOI] [PubMed] [Google Scholar]
- Artlieb U., Krepler R., Wiche G. Expression of microtubule-associated proteins, MAP-1 and MAP-2, in human neuroblastomas and differential diagnosis of immature neuroblasts. Lab Invest. 1985 Dec;53(6):684–691. [PubMed] [Google Scholar]
- Bennett G. S. Changes in intermediate filament composition during neurogenesis. Curr Top Dev Biol. 1987;21:151–183. doi: 10.1016/s0070-2153(08)60136-2. [DOI] [PubMed] [Google Scholar]
- Bernhardt R., Matus A. Initial phase of dendrite growth: evidence for the involvement of high molecular weight microtubule-associated proteins (HMWP) before the appearance of tubulin. J Cell Biol. 1982 Feb;92(2):589–593. doi: 10.1083/jcb.92.2.589. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Binder L. I., Frankfurter A., Rebhun L. I. The distribution of tau in the mammalian central nervous system. J Cell Biol. 1985 Oct;101(4):1371–1378. doi: 10.1083/jcb.101.4.1371. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bishop A. E., Power R. F., Polak J. M. Markers for neuroendocrine differentiation. Pathol Res Pract. 1988 Apr;183(2):119–128. doi: 10.1016/s0344-0338(88)80040-2. [DOI] [PubMed] [Google Scholar]
- Burgoyne R. D., Cambray-Deakin M. A., Lewis S. A., Sarkar S., Cowan N. J. Differential distribution of beta-tubulin isotypes in cerebellum. EMBO J. 1988 Aug;7(8):2311–2319. doi: 10.1002/j.1460-2075.1988.tb03074.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Caceres A., Binder L. I., Payne M. R., Bender P., Rebhun L., Steward O. Differential subcellular localization of tubulin and the microtubule-associated protein MAP2 in brain tissue as revealed by immunocytochemistry with monoclonal hybridoma antibodies. J Neurosci. 1984 Feb;4(2):394–410. doi: 10.1523/JNEUROSCI.04-02-00394.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cavanagh M. E., Parnavelas J. G. Development of somatostatin immunoreactive neurons in the rat occipital cortex: a combined immunocytochemical-autoradiographic study. J Comp Neurol. 1988 Feb 1;268(1):1–12. doi: 10.1002/cne.902680102. [DOI] [PubMed] [Google Scholar]
- Cáceres A., Banker G. A., Binder L. Immunocytochemical localization of tubulin and microtubule-associated protein 2 during the development of hippocampal neurons in culture. J Neurosci. 1986 Mar;6(3):714–722. doi: 10.1523/JNEUROSCI.06-03-00714.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dobersen M. J., Hammer J. A., Noronha A. B., MacIntosh T. D., Trapp B. D., Brady R. O., Quarles R. H. Generation and characterization of mouse monoclonal antibodies to the myelin-associated glycoprotein (MAG). Neurochem Res. 1985 Apr;10(4):499–513. doi: 10.1007/BF00964654. [DOI] [PubMed] [Google Scholar]
- Fischer I., Shea T. B., Sapirstein V. S., Kosik K. S. Expression and distribution of microtubule-associated protein 2 (MAP2) in neuroblastoma and primary neuronal cells. Brain Res. 1986 Feb;390(1):99–109. doi: 10.1016/0165-3806(86)90156-2. [DOI] [PubMed] [Google Scholar]
- Gould V. E., Wiedenmann B., Lee I., Schwechheimer K., Dockhorn-Dworniczak B., Radosevich J. A., Moll R., Franke W. W. Synaptophysin expression in neuroendocrine neoplasms as determined by immunocytochemistry. Am J Pathol. 1987 Feb;126(2):243–257. [PMC free article] [PubMed] [Google Scholar]
- Herman M. M., Perentes E., Katsetos C. D., Darcel F., Frankfurter A., Collins V. P., Donoso L. A., Eng L. F., Marangos P. J., Wiechmann A. F. Neuroblastic differentiation potential of the human retinoblastoma cell lines Y-79 and WERI-Rb1 maintained in an organ culture system. An immunohistochemical, electron microscopic, and biochemical study. Am J Pathol. 1989 Jan;134(1):115–132. [PMC free article] [PubMed] [Google Scholar]
- Herman M. M., Sipe J. C., Rubinstein L. J., Vandenberg S. R., Spence A. M., Vraa-Jensen J. An experimental mouse testicular teratoma as a model for neuroepithelial neoplasia and differentiation. II. Electron microscopy. Am J Pathol. 1975 Nov;81(2):421–444. [PMC free article] [PubMed] [Google Scholar]
- Hökfelt T., Johansson O., Goldstein M. Chemical anatomy of the brain. Science. 1984 Sep 21;225(4668):1326–1334. doi: 10.1126/science.6147896. [DOI] [PubMed] [Google Scholar]
- Katsetos C. D., Herman M. M., Frankfurter A., Gass P., Collins V. P., Walker C. C., Rosemberg S., Barnard R. O., Rubinstein L. J. Cerebellar desmoplastic medulloblastomas. A further immunohistochemical characterization of the reticulin-free pale islands. Arch Pathol Lab Med. 1989 Sep;113(9):1019–1029. [PubMed] [Google Scholar]
- Katsetos C. D., Liu H. M., Zacks S. I. Immunohistochemical and ultrastructural observations on Homer Wright (neuroblastic) rosettes and the "pale islands" of human cerebellar medulloblastomas. Hum Pathol. 1988 Oct;19(10):1219–1227. doi: 10.1016/s0046-8177(88)80155-2. [DOI] [PubMed] [Google Scholar]
- Lauder J. M., Han V. K., Henderson P., Verdoorn T., Towle A. C. Prenatal ontogeny of the GABAergic system in the rat brain: an immunocytochemical study. Neuroscience. 1986 Oct;19(2):465–493. doi: 10.1016/0306-4522(86)90275-7. [DOI] [PubMed] [Google Scholar]
- Matus A., Bernhardt R., Hugh-Jones T. High molecular weight microtubule-associated proteins are preferentially associated with dendritic microtubules in brain. Proc Natl Acad Sci U S A. 1981 May;78(5):3010–3014. doi: 10.1073/pnas.78.5.3010. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Matus A. Microtubule-associated proteins: their potential role in determining neuronal morphology. Annu Rev Neurosci. 1988;11:29–44. doi: 10.1146/annurev.ne.11.030188.000333. [DOI] [PubMed] [Google Scholar]
- McDonald J. K., Parnavelas J. G., Karamanlidis A. N., Brecha N. The morphology and distribution of peptide-containing neurons in the adult and developing visual cortex of the rat. II. Vasoactive intestinal polypeptide. J Neurocytol. 1982 Oct;11(5):825–837. doi: 10.1007/BF01153521. [DOI] [PubMed] [Google Scholar]
- McDonald J. K., Parnavelas J. G., Karamanlidis A. N., Brecha N. The morphology and distribution of peptide-containing neurons in the adult and developing visual cortex of the rat. IV. Avian pancreatic polypeptide. J Neurocytol. 1982 Dec;11(6):985–995. doi: 10.1007/BF01148312. [DOI] [PubMed] [Google Scholar]
- McDonald J. K., Parnavelas J. G., Karamanlidis A. N., Rosenquist G., Brecha N. The morphology and distribution of peptide-containing neurons in the adult and developing visual cortex of the rat. III. Cholecystokinin. J Neurocytol. 1982 Dec;11(6):881–895. doi: 10.1007/BF01148306. [DOI] [PubMed] [Google Scholar]
- McDowell J., Kitchen I. Development of opioid systems: peptides, receptors and pharmacology. Brain Res. 1987 Nov;434(4):397–421. doi: 10.1016/0165-0173(87)90006-3. [DOI] [PubMed] [Google Scholar]
- Miettinen M. Synaptophysin and neurofilament proteins as markers for neuroendocrine tumors. Arch Pathol Lab Med. 1987 Sep;111(9):813–818. [PubMed] [Google Scholar]
- Moody S. A., Quigg M. S., Frankfurter A. Development of the peripheral trigeminal system in the chick revealed by an isotype-specific anti-beta-tubulin monoclonal antibody. J Comp Neurol. 1989 Jan 22;279(4):567–580. doi: 10.1002/cne.902790406. [DOI] [PubMed] [Google Scholar]
- Mørk S. J., Rubinstein L. J. Ependymoblastoma. A reappraisal of a rare embryonal tumor. Cancer. 1985 Apr 1;55(7):1536–1542. doi: 10.1002/1097-0142(19850401)55:7<1536::aid-cncr2820550721>3.0.co;2-a. [DOI] [PubMed] [Google Scholar]
- Nunez J. Differential expression of microtubule components during brain development. Dev Neurosci. 1986;8(3):125–141. doi: 10.1159/000112248. [DOI] [PubMed] [Google Scholar]
- PIERCE G. B., Jr, DIXON F. J., Jr, VERNEY E. L. Teratocarcinogenic and tissue-forming potentials of the cell types comprising neoplastic embryoid bodies. Lab Invest. 1960 Nov-Dec;9:583–602. [PubMed] [Google Scholar]
- Palmer M. R., Miller R. J., Olson L., Seiger A. Prenatal ontogeny of neurons with enkephalin-like immunoreactivity in the rat central nervous system: an immunohistochemical mapping investigation. Med Biol. 1982 Apr;60(2):61–88. [PubMed] [Google Scholar]
- Pannese E. The histogenesis of the spinal ganglia. Adv Anat Embryol Cell Biol. 1974;47(5):7–97. doi: 10.1007/978-3-662-10338-8_2. [DOI] [PubMed] [Google Scholar]
- Pappas C. CNS myelin and synapses in a spontaneous mouse ovarian teratoma showing neural differentiation. An immunohistochemical and electron microscopic study. J Neuropathol Exp Neurol. 1981 May;40(3):289–297. doi: 10.1097/00005072-198105000-00007. [DOI] [PubMed] [Google Scholar]
- Rubinstein L. J. Diagnostic markers in human neurooncology. A progress report. Ann N Y Acad Sci. 1988;540:78–90. doi: 10.1111/j.1749-6632.1988.tb27053.x. [DOI] [PubMed] [Google Scholar]
- Sasaki A., Hirato J., Nakazato Y., Ishida Y. Immunohistochemical study of the early human fetal brain. Acta Neuropathol. 1988;76(2):128–134. doi: 10.1007/BF00688096. [DOI] [PubMed] [Google Scholar]
- Scott T., Pesce C. The ultrastructure of the nervous tissue in a benign teratoma. Acta Neuropathol. 1987;73(3):281–286. doi: 10.1007/BF00686623. [DOI] [PubMed] [Google Scholar]
- Seguela P., Geffard M., Buijs R. M., Le Moal M. Antibodies against gamma-aminobutyric acid: specificity studies and immunocytochemical results. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3888–3892. doi: 10.1073/pnas.81.12.3888. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shiosaka S., Tohyama M. Immunohistochemical techniques. Prog Brain Res. 1986;66:3–32. [PubMed] [Google Scholar]
- Sternberger L. A., Hardy P. H., Jr, Cuculis J. J., Meyer H. G. The unlabeled antibody enzyme method of immunohistochemistry: preparation and properties of soluble antigen-antibody complex (horseradish peroxidase-antihorseradish peroxidase) and its use in identification of spirochetes. J Histochem Cytochem. 1970 May;18(5):315–333. doi: 10.1177/18.5.315. [DOI] [PubMed] [Google Scholar]
- Sternberger L. A., Sternberger N. H. Monoclonal antibodies distinguish phosphorylated and nonphosphorylated forms of neurofilaments in situ. Proc Natl Acad Sci U S A. 1983 Oct;80(19):6126–6130. doi: 10.1073/pnas.80.19.6126. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stevens L. C. The development of transplantable teratocarcinomas from intratesticular grafts of pre- and postimplantation mouse embryos. Dev Biol. 1970 Mar;21(3):364–382. doi: 10.1016/0012-1606(70)90130-2. [DOI] [PubMed] [Google Scholar]
- Stevens L. C., Varnum D. S. The development of teratomas from parthenogenetically activated ovarian mouse eggs. Dev Biol. 1974 Apr;37(2):369–380. doi: 10.1016/0012-1606(74)90155-9. [DOI] [PubMed] [Google Scholar]
- Sullivan K. F. Structure and utilization of tubulin isotypes. Annu Rev Cell Biol. 1988;4:687–716. doi: 10.1146/annurev.cb.04.110188.003351. [DOI] [PubMed] [Google Scholar]
- Van Noorden S., Varndell I. A. Regulatory peptide immunocytochemistry at light- and electron microscopical levels. Experientia. 1987 Jul 15;43(7):724–734. doi: 10.1007/BF01945349. [DOI] [PubMed] [Google Scholar]
- VandenBerg S. R., May E. E., Rubinstein L. J., Herman M. M., Perentes E., Vinores S. A., Collins V. P., Park T. S. Desmoplastic supratentorial neuroepithelial tumors of infancy with divergent differentiation potential ("desmoplastic infantile gangliogliomas"). Report on 11 cases of a distinctive embryonal tumor with favorable prognosis. J Neurosurg. 1987 Jan;66(1):58–71. doi: 10.3171/jns.1987.66.1.0058. [DOI] [PubMed] [Google Scholar]
- Wallace J. A., Lauder J. M. Development of the serotonergic system in the rat embryo: an immunocytochemical study. Brain Res Bull. 1983 Apr;10(4):459–479. doi: 10.1016/0361-9230(83)90144-2. [DOI] [PubMed] [Google Scholar]