Skip to main content
SpringerLink
Log in
SpringerLink
Log in

Methods in Cellular and Molecular Pathology

  • Chapter
Endocrine Pathology

  • 160 Accesses

Abstract

In the last two decades immunohistochemical and molecular techniques have significantly contributed to our understanding of the function, differentiation, and oncogenesis of endocrine cells as well as tumor growth and biologic behavior of endocrine tumors. The purpose of this chapter is to provide an overview and introduction to some cellular and molecular methods that have been applied in diagnostic and investigative endocrine pathology. General principles and possible applications of each method are outlined, but it is beyond the scope of the chapter to provide detailed protocols. For in-depth information about specific applications we refer to publications in the literature that are cited in the text.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Coons AH, Creech HJ, Jones NR. The demonstration of pneumococcal antigen in tissue by the use of fluorescent antibody. J Immunol 1942; 256: 495–497.

    Google Scholar 

  2. Stone MJ. Monoclonal antibodies in the prehybridoma era: a brief historical perspective and personal reminiscence. Clin Lymphoma 2001; 2: 148–154.

    PubMed  CAS  Google Scholar 

  3. Kohler G, Milstein C. Continuous cultures of fused cells secreting antibody of predeifned speciifcity. Nature 1975; 256: 495–497.

    PubMed  CAS  Google Scholar 

  4. Komminoth P, Roth J, Lackie P, Bitter-Suermann D, Heitz P. Polysialic acid of the neural cell adhesion molecule distinguishes small cell lung carcinoma from carcinoids. Am J Pathol 1991; 139: 297–304.

    PubMed  CAS  Google Scholar 

  5. Heitz PU, Roth J, Zuber C, Komminoth P. Markers for neural and endocrine cells in pathology. In: Gratzl M, Langley L, eds. Markers for Neural and Endocrine Cells. Weinheim: VCH, 1991: 203–216.

    Google Scholar 

  6. Werner M, Kaloutsi V, Walter K, Buhr T, Bernhards J, Georgii A. Immunohistochemical examination of routinely processed bone marrow biopsies. Pathol Res Pract 1992; 188: 707–713.

    PubMed  CAS  Google Scholar 

  7. Werner M, von Waasielewski R, Komminoth P. Antigen retrieval, signal amplification and intensiifcation in immunohistochemistry. Histochem Cell Biol 1996; 105: 253–260.

    PubMed  CAS  Google Scholar 

  8. von Wasielewski R, Werner M, Nolte M, Wilkens L, Georgii A. Effects of antigen retrieval by microwave heating in formalin-ifxed tissue sections on a broad panel of antibodies. Histochemistry 1994; 102: 165–172.

    Google Scholar 

  9. Roth J, Saremaslani P, Zuber C. Versatility of anti-horseradish peroxidase antibody-gold complexes for cytochemistry and in-situ hybridization: preparation and application of soluble complexes with streptavidin-peroxidase conjugates and biotinylated antibodies. Histochemistry 1992; 98: 229–236.

    PubMed  CAS  Google Scholar 

  10. Roth J, Bendayan M, Orci L. Ultrastructural localization of intracellular antigens by the use of protein A–gold complex. J Histochem Cytochem 1978; 26: 1074–1081.

    PubMed  CAS  Google Scholar 

  11. Roth J, Zuber C, Komminoth P, Sata T, Li WP, Heitz PU. Applications of immunogold and lectin-gold labeling in tumor research and diagnosis. Histochem Cell Biol 1996; 106: 131–148.

    PubMed  CAS  Google Scholar 

  12. Seelentag WK, Komminoth P, Saremaslani P, Heitz PU, Roth J. CD44 isoform expression in the diffuse neuroendocrine system. I. Normal cells and hyperplasia. Histochem Cell Biol 1996; 106: 543–550.

    PubMed  CAS  Google Scholar 

  13. Roth J, Komminoth P, Heitz PU. Topographic abnormalities of pro-insulin to insulin conversion in functioning human insulinomas. Comparison of immunoelectron microscopic and clinical data. Am J Pathol 1995; 147: 489–502.

    PubMed  CAS  Google Scholar 

  14. Komminoth P, Seelentag WK, Saremaslani P, Heitz PU, Roth J. CD44 isoform expression in the diffuse neuroendocrine system. II. Benign and malignant tumors. Histochem Cell Biol 1996; 106: 551–562.

    PubMed  CAS  Google Scholar 

  15. Sternberger LA, Hardy PJ, Cuculis JJ, Meyer HG. 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; 18: 315–333.

    PubMed  CAS  Google Scholar 

  16. Cordell JL, Falini B, Erber WN, et al. Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem 1984; 32: 219–229.

    PubMed  CAS  Google Scholar 

  17. Hsu SM, Raine L, Fanger H. Use of avidin–biotin–peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 1981; 29: 577–580.

    PubMed  CAS  Google Scholar 

  18. Komminoth P. Detection of mRNA in tissue sections using digoxigenin-labeled RNA and oligonucleotide probes. In: Nonradioactive In Situ Hybridization Application Manual. Mannheim: Boehringer Mannheim, 1996: 126–135.

    Google Scholar 

  19. Adams JC. Heavy metal intensiifcation of DAB-based HRP reaction products. J Histochem Cytochem 1981; 29: 775.

    PubMed  CAS  Google Scholar 

  20. Adams JC. Biotin amplification of biotin and horseradish peroxidase signals in histochemical stains. J Histochem Cytochem 1992; 40: 1457–1463.

    PubMed  CAS  Google Scholar 

  21. Bobrow MN, Harris TD, Shaughnessy KJ, Litt GJ. Catalyzed reporter deposition, a novel method of signal amplification. Application to immunoassays. J Immunol Methods 1989; 125: 279–285.

    PubMed  CAS  Google Scholar 

  22. Komminoth P, Werner M. Target and signal ampliifcation: approaches to increase the sensitivity of in situ hybridization. Histochem Cell Biol 1997; 108: 325–333.

    PubMed  CAS  Google Scholar 

  23. Speel EJM, Saremaslani P, Roth J, Hopman AHN, Komminoth P. Improved mRNA in situ hybridization on formaldehyde-ifxed and parafifn-embedded tissue using signal ampliifcation with different haptenized tyramides. Histochem Cell Biol 1998; 110: 571–577.

    PubMed  CAS  Google Scholar 

  24. Speel EJ, Hopman AH, Komminoth P. Signal ampliifcation for DNA and mRNA. Methods Mol Biol 2000; 123: 195–216.

    PubMed  CAS  Google Scholar 

  25. Richter T, Nahrig J, Komminoth P, Kowolik J, Werner M. Protocol for ultrarapid immunostaining of frozen sections. J Clin Pathol 1999; 52: 461–463.

    PubMed  CAS  Google Scholar 

  26. Komminoth P, Roth J, Saremaslani P, Schröder S, Heitz PU. Overlapping expression of immunohistochemical markers and synaptophysin mRNA in pheochromocytomas and adrenocortical carcinomas. Implications for the differential diagnosis of adrenal gland tumors. Lab Invest 1995; 72: 424–431.

    PubMed  CAS  Google Scholar 

  27. Solcia E, Klöppel G, Sobin LH. Histological Typing of Endocrine Tumours, Vol. 23, 2nd edit. International Histological Classification of Tumours, WHO. Berlin: Springer, 2000.

    Google Scholar 

  28. Jin L, Hemperly JJ, Lloyd RV. Expression of neural cell adhesion molecule in normal and neoplastic human neuroendocrine tissues. Am J Pathol 1991; 138: 961–969.

    PubMed  CAS  Google Scholar 

  29. Komminoth P, Roth J, Saremaslani P, Matias-Guiu X, Wolfe HJ, Heitz PU. Polysialic acid of the neural cell adhesion molecule in the human thyroid: a marker for medullary thyroid carcinoma and primary C-cell hyperplasia. Am J Surg Pathol 1994; 18: 399–411.

    PubMed  CAS  Google Scholar 

  30. Erickson LA, Jin L, Wollan P, Thompson GB, van Heerden JA, Lloyd RV. Parathyroid hyperplasia, adenomas, and carcinomas: differential expression of p27Kip 1 protein. Am J Surg Pathol 1999; 23: 288–295.

    PubMed  CAS  Google Scholar 

  31. Heitz PU, von Herbay G, Kloppel G, et al. The expression of subunits of human chorionic gonadotropin (hCG) by nontrophoblastic, nonendocrine, and endocrine tumors. Am J Clin Pathol 1987; 88: 467–472.

    PubMed  CAS  Google Scholar 

  32. Oliveira AM, Tazelaar HD, Myers JL, Erickson LA, Lloyd RV. Thyroid transcription factor-1 distinguishes metastatic pulmonary from well-differentiated neuroendocrine tumors of other sites. Am J Surg Pathol 2001; 25: 815–819.

    PubMed  CAS  Google Scholar 

  33. Schröder S, Komminoth P, Padberg B, Heitz PU. Morphological typing, evaluation of tumor dignity and prognosis and etiologic classification of adrenomedullary and adrenocortical neoplasias. Pathologie 1995; 16: 307–314.

    Google Scholar 

  34. Sano T. The dispersed neuroendocrine system. In: Stefaneanu L, Sasano H, Kovacs K, eds. Molecular and Cellular Endocrine Pathology. London; Arnold, 2000: 353–373.

    Google Scholar 

  35. Lloyd RV. Applications of immunohistochemistry in the diagnosis of endocrine lesions. In: Lloyd RV, ed. Morphology Methods. Cell and Molecular Biology Methods. Totowa, NJ: Humana Press, 2001: 361–374.

    Google Scholar 

  36. Erickson LA, Jin L, Wollan PC, Thompson GB, van Heerden J, Lloyd RV. Expression of p27kip1 and Ki-67 in benign and malignant thyroid tumors. Mod Pathol 1998; 11: 169–174.

    PubMed  CAS  Google Scholar 

  37. Kimura N, Pilichowska M, Date F, Kimura I, Schindler M. Immunohistochemical expression of somatostatin type 2A receptor in neuro-endocrine tumors. Clin Cancer Res 1999; 5: 3483–3487.

    PubMed  CAS  Google Scholar 

  38. Perren A, Komminoth P, Saremaslani P, et al. Mutation and expression analyses reveal differential subcellular compartmentalization of PTEN in endocrine pancreatic tumors compared to normal islet cells. Am J Pathol 2000; 157: 1097–1103.

    PubMed  CAS  Google Scholar 

  39. Gall G, Pardue M. Formation and detection of RNA–DNA hybrid molecules in cytological preparations. Proc Natl Acad Sci USA 1969; 63: 378–381.

    PubMed  CAS  Google Scholar 

  40. Werner M, Wilkens L, Aubele M, Nolte M, Zitzelsberger H, Komminoth P. Interphase cytogenetics in pathology: principles, methods, and applications of fluorescence in situ hybridization (FISH). Histochem Cell Biol 1997; 108: 381–390.

    PubMed  CAS  Google Scholar 

  41. Höfler H, Childers H, Montminy MR, Lechan RM, Goodmann RH, Wolfe HJ. In situ hybridization methods for the detection of somatostatin mRNA in tissue sections using antisense RNA probes. Histochem J 1986; 18: 597–604.

    Google Scholar 

  42. Osamura RY, Itoh Y, Matsuno A. Applications of plastic embedding to electron microscopic immunocytochemistry and in situ hybridization in observations of production and secretion of peptide hormones. J Histochem Cytochem 2000; 48: 885–891.

    PubMed  CAS  Google Scholar 

  43. Young ID, Ailles L, Deugau K, Kisilevsky R. Transcription of cRNA for in situ hybridiziation from polymerase chain reaction-ampliifed DNA. Lab Invest 1991; 64: 709–712.

    PubMed  CAS  Google Scholar 

  44. Gall J, Pardue M. Nucleic acid hybridization in cytological preparations. Methods Enzymol 1971; 38: 470–480.

    Google Scholar 

  45. Komminoth P, Merk FB, Leav I, Wolfe HJ, Roth J. Comparison of 35S- and digoxigenin-labeled RNA and oligonucleotide probes for in situ hybridization. Expression of mRNA of the seminal vesicle secretion protein II and androgen receptor genes in the rat prostate. Histochemistry 1992; 98: 217–228.

    PubMed  CAS  Google Scholar 

  46. Komminoth P. Digoxigenin as an alternative probe labeling for in-situ hybridization. Diagn Mol Pathol 1992; 1: 142–150.

    PubMed  CAS  Google Scholar 

  47. Sperry A, Jin L, Lloyd RV. Microwave treatment enhances detection of RNA and DNA by in situ hybridization. Diagn Mol Pathol 1996; 5: 291–296.

    PubMed  CAS  Google Scholar 

  48. Long AA, Mueller J, Andre-Schwartz J, Barrett K, Schwartz R, Wolfe H. High-speciifcity in-situ hybridization: methods and application. Diagn Mol Pathol 1992; 1: 45–57.

    PubMed  CAS  Google Scholar 

  49. Werner M, Wilkens L, Nasarek A, Tchinda J, Komminoth P. Detection of karyotype changes in interphase cells: oligonucleotide-primed in situ labelling versus fluorescence in situ hybridization. Virchows Arch 1997; 430: 381–387.

    PubMed  CAS  Google Scholar 

  50. Haase AT, Retzel EF, Staskus KA. Ampliifcation and detection of lentiviral DNA inside cells. Proc Natl Acad Sci USA 1990; 87: 4971–4975.

    PubMed  CAS  Google Scholar 

  51. Ray R, Komminoth P, Machado M, Wolfe HJ. Combined polymerase chain reaction and in-situ hybridization for the detection of single copy genes and viral genomic sequences in intact cells. Mod Pathol 1991; 4: 124A.

    Google Scholar 

  52. Komminoth P, Long AA, Ray R, Wolfe HJ. In situ polymerase chain reaction detection of viral DNA, single copy genes and gene rearrangements in cell suspensions and cytospins. Diagn Mol Pathol 1992; 1: 85–97.

    PubMed  CAS  Google Scholar 

  53. Nuovo G, MacConnell P, Forde A, Delvenne P. Detection of human papillomavirus DNA in formalin-ifxed tissues by in situ hybridization after amplification by polymerase chain reaction. Am J Pathol 1991; 139: 847–854.

    PubMed  CAS  Google Scholar 

  54. Spann W, Pachmann K, Zabnienska H, Pielmeier A, Emmerich B. In situ ampliifcation of single copy gene segments in individual cells by the polymerase chain reaction. Infection 1991; 19: 242–244.

    PubMed  CAS  Google Scholar 

  55. Komminoth P, Long AA. In-situ polymerase chain reaction. An overview of methods, applications and limitations of a new molecular technique. Virchows Arch [B] 1993; 64: 67–73.

    CAS  Google Scholar 

  56. Long AA, Komminoth P, Lee E, Wolfe HJ. Comparison of indirect and direct in-situ polymerase chain reaction in cell preparations and tissue sections. Detection of viral DNA, gene rearrangements and chromosomal translocations. Histochemistry 1993; 99: 151–162.

    PubMed  CAS  Google Scholar 

  57. Komminoth P, Long AA. In-situ polymerase chain reaction—methodology, applications and non-speciifc pathways. In: PCR Application Manual. Mannheim: Boehringer Mannheim, 1995: 97–106.

    Google Scholar 

  58. Komminoth P, Long AA. In situ polymerase chain reaction and its applications to the study of endocrine diseases. Endocr Pathol 1995; 6: 167–171.

    Google Scholar 

  59. Embretson J, Zupancic M, Beneke J, et al. Analysis of human immunodeficiency virus-infected tissues by ampliifcation and in situ hybridization reveals latent and permissive infections at single-cell resolution. Proc Natl Acad Sci USA 1993; 90: 357–361.

    PubMed  CAS  Google Scholar 

  60. Long AA, Komminoth P. In situ polymerase chain reaction: an overview. In: Gosden JR, ed. Methods in Molecular Biology, Vol. XX. Protocols for PRINS and In Situ PCR. Totowa, NJ: Humana Press, 1997: 141–161.

    Google Scholar 

  61. Long AA, Komminoth P, Wolfe HJ. Detection of HIV provirus by in situ polymerase chain reaction (letter). N Engl Med J 1992; 327: 1529.

    CAS  Google Scholar 

  62. Zaki SR, Heneine W, Cofifeld LM, Greer PW, Sinha SD, Folks TM. In-situ polymerase chain reaction: applications and current limitations. AIDS 1994; 8: 1186–1188.

    CAS  Google Scholar 

  63. Höfler H. In situ polymerase chain reaction: toy or tool? (Editorial). Histochemistry 1993; 99: 103–104.

    PubMed  Google Scholar 

  64. Höfler H, Pütz B, Mueller J, Neubert W, Sutter G, Gais P. In situ ampliifcation of measles virus RNA by the self-sustained sequence replication reaction. Lab Invest 1995; 73: 577–585.

    PubMed  Google Scholar 

  65. Zehbe I, Hacker GW, Sällström JF, Rylander E, Wilander E. Self-sustained sequence replication-based ampliifcation (3SR) for the in-situ detection of mRNA in cultured cells. Cell Vision 1994; 1: 20–24.

    CAS  Google Scholar 

  66. Mogensen J, Kolvraa S, Hindkjaer J, et al. Non-radioactive sequence speciifc detection of RNA in situ by primed in situ labelling (PRINS). Exp Cell Res 1991; 196: 92–98.

    PubMed  CAS  Google Scholar 

  67. Raap AK, Van de Corput MPC, Vervenne RAW, van Gijlswijk RPM, Tanke HJ, Wiegant J. Ultra-sensitive FISH using peroxidase-mediated deposition of biotin-or fluorochrome tyramides. Hum Mol Genet 1995; 4: 529–534.

    PubMed  CAS  Google Scholar 

  68. Qian X, Bauer RA, Xu HS, Lloyd RV. In situ hybridization detection of calcitonin mRNA in routinelyixed, parafifn-embedded tissue sections: a comparison of different types of probes combined with tyramide signal ampliifcation. Appl Immunohistochem Mol Morphol 2001; 9: 61–69.

    PubMed  CAS  Google Scholar 

  69. Hopman AHN, Ramaekers FCS, Speel EJM. Rapid synthesis of biotin-, digoxigenin-, trinitrophenyl-, and fluorochrome-labeled tyramides and their application for in situ hybridization using CARD-amplification. J Histochem Cytochem 1998; 46: 771–777.

    PubMed  CAS  Google Scholar 

  70. Speel EJ, Hopman AH, Komminoth P. Ampliifcation methods to increase the sensitivity of in situ hybridization: play card(s). J Histochem Cytochem 1999; 47: 281–288.

    PubMed  CAS  Google Scholar 

  71. Ikeo Y, Sakurai A, Suzuki R, et al. Proliferation-associated expression of the MEN1 gene as revealed by in situ hybridization: possible role of the menin as a negative regulator of cell proliferation under DNA damage. Lab Invest 2000; 80: 797–804.

    PubMed  CAS  Google Scholar 

  72. Jacobsson G, Bean AJ, Scheller RH, et al. Identiifcation of synaptic proteins and their isoform mRNAs in compartments of pancreatic endocrine cells. Proc Natl Acad Sci USA 1994; 91: 12487–12491.

    PubMed  CAS  Google Scholar 

  73. McKenzie KJ, Hind C, Farquharson MA, McGill M, Foulis AK. Demonstration of insulin production and storage in insulinomas by in situ hybridization and immunocytochemistry. J Pathol 1997; 181: 218–222.

    PubMed  CAS  Google Scholar 

  74. Farnebo F, Enberg U, Grimelius L, et al. Tumor-speciifc decreased expression of calcium sensing receptor messenger ribonucleic acid in sporadic primary hyperparathyroidism. J Clin Endocrinol Metab 1997; 82: 3481–3486.

    PubMed  CAS  Google Scholar 

  75. Filipsson K, Sundler F, Hannibal J, Ahren B. PACAP and PACAP receptors in insulin producing tissues: localization and effects. Regul Pept 1998; 74: 167–175.

    PubMed  CAS  Google Scholar 

  76. Luts L, Bergenfelz A, Alumets J, Sundler F. Parathyroid function and histology in patients with parathyroid adenoma: correlation of clinical and morphologic ifndings. World J Surg 1997; 21: 553–563.

    PubMed  CAS  Google Scholar 

  77. Lloyd RV, Jin L. In situ hybridization analysis of chromogranin A and B mRNAs in neuroendocrine tumors with digoxigeninlabeled oligonucleotide probe cocktails. Diagn Mol Pathol 1995; 4: 143–151.

    PubMed  CAS  Google Scholar 

  78. Lloyd RV, Fields K, Jin L, Horvath E, Kovacs K. Analysis of endocrine active and clinically silent corticotropic adenomas by in situ hybridization. Am J Pathol 1990; 137: 479–488.

    PubMed  CAS  Google Scholar 

  79. DeLellis RA, Wolfe HJ. Contributions of immunohistochemical and molecular biological techniques to endocrine pathology. J Histochem Cytochem 1987; 35: 1347–1351.

    PubMed  CAS  Google Scholar 

  80. Lloyd RV, Jin L, Kulig E, Fields K. Molecular approaches for the analysis of chromogranins and secretogranins. Diagn Mol Pathol 1992; 1: 2–15.

    PubMed  CAS  Google Scholar 

  81. Boultwood J, Wynford-Thomas D, Richards GP, Craig RK, Williams ED. In-situ analysis of calcitonin and CGRP expression in medullary thyroid carcinoma. Clin Endocrinol (Oxf) 1990; 33: 381–390.

    CAS  Google Scholar 

  82. Hofler H, Putz B, Ruhri C, Wirnsberger G, Klimpifnger M, Smolle J. Simultaneous localization of calcitonin mRNA and peptide in a medullary thyroid carcinoma. Virchows Arch [B] Cell Pathol Mol Pathol 1987; 54: 144–151.

    CAS  Google Scholar 

  83. Kendall CH, Roberts PA, Pringle JH, Lauder I. The expression of parathyroid hormone messenger RNA in normal and abnormal parathyroid tissue. J Pathol 1991; 165: 111–118.

    PubMed  CAS  Google Scholar 

  84. Baz E, Saeger W, Uhlig H, Fehr S, Ludecke DK. HGH, PRL and beta HCG/beta LH gene expression in clinically inactive pituitary adenomas detected by in situ hybridization. Virchows Arch [A] Pathol Anat Histopathol 1991; 418: 405–410.

    CAS  Google Scholar 

  85. Larsson LI, Hougaard DM. Combined non-radioactive detection of peptide hormones and their mRNAís in endocrine cells. Histochemistry 1991; 96: 375–380.

    PubMed  CAS  Google Scholar 

  86. Trembleau A, Roche D, Calas A. Combination of non-radioactive and radioactive in situ hybridization with immunohistochemistry: a new method allowing the simultaneous detection of two mRNAs and one antigen in the same brain tissue section. J Histochem Cytochem 1993; 41: 489–498.

    PubMed  CAS  Google Scholar 

  87. Volante M, Allia E, Gugliotta P, et al. Expression of ghrelin and of the GH secretagogue receptor by pancreatic islet cells and related endocrine tumors. J Clin Endocrinol Metab 2002; 87: 1300–1308.

    PubMed  CAS  Google Scholar 

  88. Chaudhry A, Funa K, Oberg K. Expression of growth factor peptides and their receptors in neuroendocrine tumors of the digestive system. Acta Oncol 1993; 32: 107–114.

    PubMed  CAS  Google Scholar 

  89. Cunningham JL, Lopez-Egido JR, Janson ET, Eriksson B, Oberg K, Gobl AE. Transmembrane protein tyrosine phosphatase IA-2 (ICA 512) is expressed in human midgut carcinoids but is not detectable in normal enterochromafifn cells. J Endocrinol 2000; 164: 315–322.

    PubMed  CAS  Google Scholar 

  90. Hoog A, Kjellman M, Nordqvist AC, et al. Insulin-like growth factor-II in endocrine pancreatic tumours. Immunohistochemical, biochemical and in situ hybridization findings. Apmis 2001;109: 127–140.

    Google Scholar 

  91. Hunziker E, Stein M. Nestin-expressing cells in the pancreatic islets of Langerhans. Biochem Biophys Res Commun 2000; 271: 116–119.

    PubMed  CAS  Google Scholar 

  92. Lemmens IH, Forsberg L, Pannett AA, et al. Menin interacts directly with the homeobox-containing protein Pem. Biochem Biophys Res Commun 2001; 286: 426–431.

    PubMed  CAS  Google Scholar 

  93. Southern EM. Detection of speciifc sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 1975; 98: 503–517.

    PubMed  CAS  Google Scholar 

  94. Whetsell L, Maw G, Nadon N, Ringer DP, Schaefer FV. Polymerase chain reaction microanalysis of tumors from stained histological slides. Oncogene 1992; 7: 2355–2361.

    PubMed  CAS  Google Scholar 

  95. Perren A, Roth J, Muletta-Feurer S, et al. Clonal analysis of sporadic pancreatic endocrine tumours. J Pathol 1998; 186: 363–371.

    PubMed  CAS  Google Scholar 

  96. Srinivasan R. Ablation of polymers and biological tissue by ultraviolet lasers. Science 1986; 234: 559–565.

    PubMed  CAS  Google Scholar 

  97. Greulich KO, Weber G. The light microscope on its way from an analytical to a preparative tool. J Microsc 1992; 162: 127–151.

    Google Scholar 

  98. de With A, Greulich KO. Wavelength dependence of laser-induced DNA damage in lymphocytes observed by single-cell gel electrophoresis. J Photochem Photobiol B 1995; 30: 71–76.

    PubMed  Google Scholar 

  99. Becker I, Becker KF, Rohrl MH, Minkus G, Schutze K, Hofler H. Single-cell mutation analysis of tumors from stained histologic slides. Lab Invest 1996; 75: 801–807.

    PubMed  CAS  Google Scholar 

  100. Schutze K, Lahr G. Identification of expressed genes by laser-mediated manipulation of single cells. Nat Biotechnol 1998; 16: 737–742.

    PubMed  CAS  Google Scholar 

  101. Bohm M, Wieland I, Schutze K, Rubben H. Microbeam MOMeNT: non-contact laser microdissection of membrane-mounted native tissue. Am J Pathol 1997; 151: 63–67.

    PubMed  CAS  Google Scholar 

  102. Volante M, Papotti M, Roth J, et al. Mixed medullary-follicular thyroid carcinoma. Molecular evidence for a dual origin of tumor components. Am J Pathol 1999; 155: 1499–1509.

    PubMed  CAS  Google Scholar 

  103. Simone NL, Bonner RF, Gillespie JW, Emmert-Buck MR, Liotta LA. Laser-capture microdissection: opening the microscopic frontier to molecular analysis. Trends Genet 1998; 14: 272–276.

    PubMed  CAS  Google Scholar 

  104. Burton MP, Schneider BG, Brown R, Escamilla-Ponce N, Gulley ML. Comparison of histologic stains for use in PCR analysis of microdissected, paraffin-embedded tissues. BioTechniques 1998; 24: 86–92.

    PubMed  CAS  Google Scholar 

  105. Fend F, Emmert-Buck MR, Chuaqui R, et al. Immuno-LCM: laser capture microdissection of immunostained frozen sections for mRNA analysis. Am J Pathol 1999; 154: 61–66.

    PubMed  CAS  Google Scholar 

  106. Ponten F, Williams C, Ling G, et al. Genomic analysis of single cells from human basal cell cancer using laser-assisted capture microscopy. Mutat Res 1997; 382: 45–55.

    PubMed  CAS  Google Scholar 

  107. Hiller T, Snell L, Watson PH. Microdissection RT-PCR analysis of gene expression in pathologically deifned frozen tissue sections. BioTechniques 1996;21:38–40, 42, 44.

    Google Scholar 

  108. Aubele M, Zitzelsberger H, Schenck U, Walch A, Hofler H, Werner M. Distinct cytogenetic alterations in squamous intraepithelial lesions of the cervix revealed by laser-assisted microdissection and comparative genomic hybridization. Cancer 1998; 84: 375–379.

    PubMed  CAS  Google Scholar 

  109. Goldsworthy SM, Stockton PS, Trempus CS, Foley JF, Maronpot RR. Effects of fixation on RNA extraction and ampliifcation from laser capture microdissected tissue. Mol Carcinogen 1999; 25: 86–91.

    CAS  Google Scholar 

  110. Specht MC, Tucker ON, Hocever M, Gonzalez D, Teng L, Fahey TJ 3rd. Cyclooxygenase-2 expression in thyroid nodules. J Clin Endocrinol Metab 2002; 87: 358–363.

    PubMed  CAS  Google Scholar 

  111. Telenius H, Pelmear AH, Tunnacliffe A, et al. Cytogenetic analysis by chromosome painting using DOP-PCR amplified flow-sorted chromosomes. Genes Chromosomes Cancer 1992; 4: 257–263.

    PubMed  CAS  Google Scholar 

  112. Specht K, Richter T, Muller U, Walch A, Werner M, Hofler H. Quantitative gene expression analysis in microdissected archival formalin-fixed and parafifn-embedded tumor tissue. Am J Pathol 2001; 158: 419–429.

    PubMed  CAS  Google Scholar 

  113. Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 1977;74:5463– 5467.

    Google Scholar 

  114. Wilson RK, Chen C, Avdalovic N, Burns J, Hood L. Development of an automated procedure for fluorescent DNA sequencing. Genomics 1990; 6: 626–634.

    PubMed  CAS  Google Scholar 

  115. Orita M, Suzuki Y, Sekiya T, Hayashi K. Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction. Genomics 1989; 5: 874–879.

    PubMed  CAS  Google Scholar 

  116. Görtz B, Roth J, Krähenmann A, et al. Mutations and allelic deletions of the MEN1 gene are associated with a subset of sporadic endocrine pancreatic and neuroendocrine tumors and not restricted to foregut neoplasms. Am J Pathol 1999; 154: 429–436.

    PubMed  Google Scholar 

  117. Hiort O, Wodtke A, Struve D, Zöllner A, Sinnecker GHG. Detection of point mutations in the androgen receptor gene using non-isotopic single strand conformation polymorphism analysis. Hum Mol Genet 1994; 3: 1163–1166.

    PubMed  CAS  Google Scholar 

  118. Abrams ES, Murdaugh SE, Lerman LS. Comprehensive detection of single base changes in human genomic DNA using denaturing gradient gel electrophoresis and a GC clamp. Genomics 1990; 7: 463–475.

    PubMed  CAS  Google Scholar 

  119. Kishi M, Tsukada T, Shimizu S, et al. A large germline deletion of the MEN1 gene in a family with multiple endocrine neoplasia type 1. Jpn J Cancer Res 1998; 89: 1–5.

    PubMed  CAS  Google Scholar 

  120. Pack SD, Zbar B, Pak E, et al. Constitutional von Hippel-Lindau (VHL) gene deletions detected in VHL families by fluorescence in situ hybridization. Cancer Res 1999; 59: 5560–5564.

    PubMed  CAS  Google Scholar 

  121. Komminoth P, Muletta-Feurer S, Seelentag WKF, Roth J, Heitz PU. Analysis of RET proto-oncogene mutations in Swiss families with multiple endocrine neoplasia type 2. Hered Cancer 1996; 108–118.

    Google Scholar 

  122. Komminoth P. Multiple endokrine Neoplasie Typ 1 und 2. Diagnostische Leitlinien und molekulare Pathologie 1997. Pathologie 1997; 18: 286–300.

    CAS  Google Scholar 

  123. van der Harst E, de Krijger RR, Bruining HA, et al. Prognostic value of RET proto-oncogene point mutations in malignant and benign, sporadic phaeochromocytomas. Int J Cancer 1998; 79: 537–540.

    PubMed  Google Scholar 

  124. Knudson AG Jr, Hethcote HW, Brown BW. Mutation and childhood cancer: a probabilistic model for the incidence of retinoblastoma. Proc Natl Acad Sci USA 1975; 72: 5116–5120.

    PubMed  Google Scholar 

  125. Cavenee WK, Dryja TP, Phillips RA, et al. Expression of recessive alleles by chromosomal mechanisms in retinoblastoma. Nature 1983; 305: 779–784.

    PubMed  CAS  Google Scholar 

  126. Cawkwell L, Bell SM, Lewis FA, Dixon MF, Taylor GR, Quirke P. Rapid detection of allele loss in colorectal tumours using micro-satellites and fluorescent DNA technology. Br J Cancer 1993; 67: 1262–1267.

    PubMed  CAS  Google Scholar 

  127. Barghorn A, Komminoth P, Bachmann D, et al. Deletion at 3p25.3- p23 is frequently encountered in endocrine pancreatic tumours and is associated with metastatic progression. J Pathol 2001; 194: 451–458.

    PubMed  CAS  Google Scholar 

  128. Barghorn A, Speel EJ, Farspour B, et al. Putative tumor suppressor loci at 6q22 and 6q23–q24 are involved in the malignant progression of sporadic endocrine pancreatic tumors. Am J Pathol 2001; 158: 1903–1911.

    PubMed  CAS  Google Scholar 

  129. Görtz B, Roth J, Speel EJM, et al. MEN1 gene mutation analysis of sporadic adrenocortical lesions. Int J Cancer 1999; 80: 373–379.

    PubMed  Google Scholar 

  130. Speel E, Meier D, Matter C, et al. Chromosome 1 1q losses in sporadic endocrine pancreatic tumors: another tumor suppressor gene telomeric of MEN1? Virchow Arch 1999 435, 219 (Abstr P-105).

    Google Scholar 

  131. Perren A, Schmid S, Saremaslani P, et al. The role of the succinatedehydrogenase-D (SDHD) tumor suppressor gene on 1 1q23 in sporadic endocrine tumors. Verh Dtsch Ges Path 2001; 85: 275–278.

    Google Scholar 

  132. Pinkel D, Segraves R, Sudar D, et al. High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nat Genet 1998; 20: 207–211.

    PubMed  CAS  Google Scholar 

  133. Solinas-Toldo S, Lampel S, Stilgenbauer S, et al. Matrix-based comparative genomic hybridization: biochips to screen for genomic im-balances. Genes Chromosomes Cancer 1997; 20: 399–407.

    PubMed  CAS  Google Scholar 

  134. Pollack JR, Perou CM, Alizadeh AA, et al. Genome-wide analysis of DNA copy-number changes using cDNA microarrays. Nat Genet 1999; 23: 41–46.

    PubMed  CAS  Google Scholar 

  135. Zhao J, Roth J, Bode-Lesniewska B, Pfaltz M, Heitz PU, Komminoth P. Combined comparative genomic hybridization and genomic microarray for detection of gene ampliifcations in pulmonary artery intimal sarcomas and adrenocortical tumors. Genes Chromosomes Cancer 2002; 34: 48–57.

    PubMed  CAS  Google Scholar 

  136. Sgroi DC, Teng S, Robinson G, LeVangie R, Hudson JR Jr, Elkahloun AG. In vivo gene expression profile analysis of human breast cancer progression. Cancer Res 1999; 59: 5656–5661.

    PubMed  CAS  Google Scholar 

  137. Leethanakul C, Patel V, Gillespie J, et al. Distinct pattern of expression of differentiation and growth-related genes in squamous cell carcinomas of the head and neck revealed by the use of laser capture microdissection and cDNA arrays. Oncogene 2000; 19: 3220–3224.

    PubMed  CAS  Google Scholar 

  138. Lyon M. Gene action in the X-chromosome of the mouse (Mus musculus L.). Nature 1961; 190: 372–373.

    PubMed  CAS  Google Scholar 

  139. Gartler SM, Riggs AD. Mammalian X-chromosome inactivation. Annu Rev Genet 1983; 17: 155–190.

    PubMed  CAS  Google Scholar 

  140. Tsukada M, Wada Y, Hamade N, Masuda H, Koizumi A. Stable Lyonization of X-linked pgk-1 gene during aging in normal tissues and tumors of mice carrying Searle’s translocation. J Gerontol 1991; 46: B213–B216.

    PubMed  CAS  Google Scholar 

  141. Fialkow PJ. Glucose-6-phosphate dehydrogenase (G-6-PD) markers in Burkitt lymphoma and other malignancies. Hamatol Bluttrans-fus 1977; 20: 297–305.

    CAS  Google Scholar 

  142. Vogelstein B, Fearon ER, Hamilton SR, Feinberg AP. Use of restriction fragment length polymorphisms to determine the clonal origin of human tumors. Science 1985; 227: 642–645.

    PubMed  CAS  Google Scholar 

  143. Tilley WD, Marcelli M, Wilson JD, McPhaul MJ. Characterization and expression of a cDNA encoding the human androgen receptor. Proc Natl Acad Sci USA 1989; 86: 327–331.

    PubMed  CAS  Google Scholar 

  144. Kubota T, Nonoyama S, Tonoki H, et al. A new assay for the analysis of X-chromosome inactivation based on methylation-specific PCR. Hum Genet 1999; 104: 49–55.

    PubMed  CAS  Google Scholar 

  145. Harrison CN, Gale RE, Linch DC. Quantification of X-chromosome inactivation patterns using RT-PCR of the polymorphic iduronate-2-sulphatase gene and correlation of the results obtained with DNA-based techniques. Leukemia 1998; 12: 1834–1839.

    PubMed  CAS  Google Scholar 

  146. Derwahl M, Studer H. Hyperplasia versus adenoma in endocrine tissues: are they different? Trends Endocrinol Metab 2002; 13: 23–28.

    PubMed  CAS  Google Scholar 

  147. Noguchi S, Motomura K, Inaji H, Imaoka S, Koyama H. Clonal analysis of parathyroid adenomas by means of the polymerase chain reaction. Cancer Lett 1994; 78: 93–97.

    PubMed  CAS  Google Scholar 

  148. Arnold A, Staunton CE, Kim HG, Gaz RD, Kronenberg HM. Monoclonality and abnormal parathyroid hormone genes in parathyroid adenomas. N Engl J Med 1988; 318: 658–662.

    PubMed  CAS  Google Scholar 

  149. Ferraris AM, Mangerini R, Gaetani GF, Romei C, Pinchera A, Pacini F. Polyclonal origin of medullary carcinoma of the thyroid in multiple endocrine neoplasia type 2. Hum Genet 1997; 99: 202–205.

    PubMed  CAS  Google Scholar 

  150. Missiaglia E, Moore PS, Williamson J, et al. Sex chromosome anomalies in pancreatic endocrine tumors. Int J Cancer 2002; 98: 532–538.

    PubMed  CAS  Google Scholar 

  151. Speel EJ, Scheidweiler AF, Zhao J, et al. Genetic evidence for early divergence of small functioning and nonfunctioning endocrine pancreatic tumors: gain of 9Q34 is an early event in insulinomas. Cancer Res 2001; 161: 5186–5192.

    Google Scholar 

  152. Speel EJ, Richter J, Moch H, et al. Genetic differences in endocrine pancreatic tumor subtypes detected by comparative genomic hybridization. Am J Pathol 1999; 155: 1787–1794.

    PubMed  CAS  Google Scholar 

  153. Stratakis CA, Schussheim DH, Freedman SM, et al. Pituitary macro-adenoma in a 5-year-old: an early expression of multiple endocrine neoplasia type 1. J Clin Endocrinol Metab 2000; 85: 4776–4780.

    PubMed  CAS  Google Scholar 

  154. Corvi R, Martinez-Alfaro M, Harach HR, Zini M, Papotti M, Romeo G. Frequent RET rearrangements in thyroid papillary microcarcinoma detected by interphase fluorescence in situ hybridization. Lab Invest 2001; 81: 1639–1645.

    PubMed  CAS  Google Scholar 

  155. Salassidis K, Bruch J, Zitzelsberger H, Lengfelder E, Kellerer AM, Bauchinger M. Translocation t(10;14)(q1 1.2:q22.1) fusing the kinetin to the RET gene creates a novel rearranged form (PTC8) of the RET proto-oncogene in radiation-induced childhood papillary thyroid carcinoma. Cancer Res 2000; 60: 2786–2789.

    PubMed  CAS  Google Scholar 

  156. Roque L, Serpa A, Clode A, Castedo S, Soares J. Significance of trisomy 7 and 12 in thyroid lesions with follicular differentiation: a cytogenetic and in situ hybridization study. Lab Invest 1999; 79: 369–378.

    PubMed  CAS  Google Scholar 

  157. Finelli P, Giardino D, Rizzi N, et al. Non-random trisomies of chromosomes 5, 8 and 12 in the prolactinoma sub-type of pituitary adenomas: conventional cytogenetics and interphase FISH study. Int J Cancer 2000; 86: 344–350.

    PubMed  CAS  Google Scholar 

  158. Kontogeorgos G, Kapranos N, Orphanidis G, Rologis D, Kokka E. Molecular cytogenetics of chromosome 11 in pituitary adenomas: a comparison of fluorescence in situ hybridization and DNA ploidy study. Hum Pathol 1999; 30: 1377–1382.

    PubMed  CAS  Google Scholar 

  159. Huang SC, Koch CA, Vortmeyer AO, et al. Duplication of the mutant RET allele in trisomy 10 or loss of the wild-type allele in multiple endocrine neoplasia type 2-associated pheochromocytomas. Cancer Res 2000; 60: 6223–6226.

    PubMed  CAS  Google Scholar 

  160. Takano T, Hasegawa Y, Miyauchi A, et al. Overexpression of kalpha1 tubulin mRNA in thyroid anaplastic carcinoma. Cancer Lett 2001; 168: 51–55.

    PubMed  CAS  Google Scholar 

  161. Bieche I, Franc B, Vidaud D, Vidaud M, Lidereau R. Analyses of MYC, ERBB2, and CCND1 genes in benign and malignant thyroid follicular cell tumors by real-time polymerase chain reaction. Thyroid 2001; 11: 147–152.

    PubMed  CAS  Google Scholar 

  162. Knerr I, Schuster S, Nomikos P, et al. Gene expression of adrenomedullin, leptin, their receptors and neuropeptide Y in hormone-secreting and non-functioning pituitary adenomas, meningiomas and malignant intracranial tumours in humans. Neuropathol Appl Neurobiol 2001; 27: 215–222.

    PubMed  CAS  Google Scholar 

  163. Bhuiyan MM, Sato M, Murao K, et al. Differential expression of menin in various adrenal tumors. The role of menin in adrenal tumors. Cancer 2001; 92: 1393–1401.

    PubMed  CAS  Google Scholar 

  164. Suwa T, Yang L, Hornsby PJ. Telomerase activity in primary cultures of normal adrenocortical cells. J Endocrinol 2001; 170: 677–684.

    PubMed  CAS  Google Scholar 

  165. Goebel SU, Peghini PL, Goldsmith PK, et al. Expression of the calcium-sensing receptor in gastrinomas. J Clin Endocrinol Metab 2000; 85: 4131–4137.

    PubMed  CAS  Google Scholar 

  166. Lam KY, Leung PS. Regulation and expression of a renin–angiotensin system in human pancreas and pancreatic endocrine tumours. Eur J Endocrinol 2002; 146: 567–572.

    PubMed  CAS  Google Scholar 

  167. Kjellman P, Lagercrantz S, Hoog A, Wallin G, Larsson C, Zedenius J. Gain of 1q and loss of 9q21.3–q32 are associated with a less favorable prognosis in papillary thyroid carcinoma. Genes Chromosomes Cancer 2001;32:43–49.

    Google Scholar 

  168. Frisk T, Zedenius J, Lundberg J, Wallin G, Kytola S, Larsson C. CGH alterations in medullary thyroid carcinomas in relation to the RET M918T mutation and clinical outcome. Int J Oncol 2001; 18: 1219–1225.

    PubMed  CAS  Google Scholar 

  169. Wilkens L, Benten D, Tchinda J, et al. Aberrations of chromosomes 5 and 8 as recurrent cytogenetic events in anaplastic carcinoma of the thyroid as detected by fluorescence in situ hybridisation and com- parative genomic hybridisation. Virchows Arch 2000; 436: 312–318

    PubMed  CAS  Google Scholar 

  170. Komoike Y, Tamaki Y, Sakita I, et al. Comparative genomic hybridization deifnes frequent loss on 16p in human anaplastic thyroid carcinoma. Int J Oncol 1999; 14: 1157–1162.

    PubMed  CAS  Google Scholar 

  171. Hemmer S, Wasenius VM, Knuutila S, Joensuu H, Franssila K. Comparison of benign and malignant follicular thyroid tumours by comparative genomic hybridization. Br J Cancer 1998; 78: 1012–1017.

    PubMed  CAS  Google Scholar 

  172. Trautmann K, Thakker RV, Ellison DW, et al. Chromosomal aberrations in sporadic pituitary tumors. Int J Cancer 2001;91:809– 814.

    Google Scholar 

  173. Daniely M, Aviram A, Adams EF, et al. Comparative genomic hybridization analysis of nonfunctioning pituitary tumors. J Clin Endocrinol Metab 1998; 83: 1801–1805.

    PubMed  CAS  Google Scholar 

  174. Dannenberg H, de Krijger RR, Zhao J, et al. Differential loss of chromosome 1 1q in familial and sporadic parasympathetic paragangliomas detected by comparative genomic hybridization. Am J Pathol 2001; 158: 1937–1942.

    PubMed  CAS  Google Scholar 

  175. Dannenberg H, Speel EJ, Zhao J, et al. Losses of chromosomes 1p and 3q are early genetic events in the development of sporadic pheochromocytomas. Am J Pathol 2000; 157: 353–359.

    PubMed  CAS  Google Scholar 

  176. Dohna M, Reincke M, Mincheva A, Allolio B, Solinas-Toldo S, Lichter P. Adrenocortical carcinoma is characterized by a high frequency of chromosomal gains and high-level ampliifcations. Genes Chromosomes Cancer 2000; 28: 145–152.

    PubMed  CAS  Google Scholar 

  177. Huang Y, Prasad M, Lemon WJ, et al. Gene expression in papillary thyroid carcinoma reveals highly consistent proifles. Proc Natl Acad Sci USA 2001; 98: 15044–15049.

    PubMed  CAS  Google Scholar 

  178. Evans CO, Young AN, Brown MR, et al. Novel patterns of gene expression in pituitary adenomas identiifed by complementary deoxyribonucleic acid microarrays and quantitative reverse transcription-polymerase chain reaction. J Clin Endocrinol Metab 2001; 86: 3097–3107.

    PubMed  CAS  Google Scholar 

  179. Hodgson G, Hager JH, Volik S, et al. Genome scanning with array CGH delineates regional alterations in mouse islet carcinomas. Nat Genet 2001; 29: 459–464.

    PubMed  CAS  Google Scholar 

Download references

Authors
  1. Paul Komminoth MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aurel A. Perren MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Axel Walch MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Martin Werner MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Pathology, Mayo Clinic, Rochester, MN, USA

    Ricardo V. Lloyd MD, PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Springer Science+Business Media New York

About this chapter

Cite this chapter

Komminoth, P., Perren, A.A., Walch, A., Werner, M. (2004). Methods in Cellular and Molecular Pathology. In: Lloyd, R.V. (eds) Endocrine Pathology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-403-0_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-403-0_1

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-423-4

  • Online ISBN: 978-1-59259-403-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation