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Molekularpathologie der malignen Tumoren des Ösophagus

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Pathologie

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Zusammenfassung

Das Kapitel fasst das Wissen um die molekularpathologischen Prozesse zusammen, die bei der Entstehung und Progression von Ösophaguskarzinomen eine Rolle spielen. In Zusammenschau mit der Histologie der Vorläuferläsionen werden prognostische und therapierelevante prädiktive Aussagen gemacht. Bei fortgeschrittenen Karzinomen werden prädiktive Marker für eine HER2/neu, EGFR- und MET-gerichtete Therapie, wie etwa HER2/neu und MET-Genamplifikation sowie Proteinüberexpression oder EGFR- bzw. KRAS-Mutationstatus, erörtert.

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Literatur

  1. Alvarez H, Opalinska J, Zhou L, Sohal D, Fazzari MJ, Yu Y, Montagna C, Montgomery EA, Canto M, Dunbar KB, Wang J, Roa JC, Mo Y, Bhagat T, Ramesh KH, Cannizzaro L, Mollenhauer J, Thompson RF, Suzuki M, Meltzer SJ, Melnick A, Greally JM, Maitra A, Verma A (2011) Widespread hypomethylation occurs early and synergizes with gene amplification during esophageal carcinogenesis. PLoS Genet 7: (e1001356)

    Google Scholar 

  2. Annals of the New Academy of Sciences Barrett's Esophagus (Hrsg) (2011) The 10th OESO World Congress Proceedings. September 2011. Bd 1232. The New York Academy of Sciences, New York, S 1–421 (S vii–viii)

    Google Scholar 

  3. Chan JA, Blaszkowsky LS, Enzinger PC, Ryan DP, Abrams TA, Zhu AX, Temel JS, Schrag D, Bhargava P, Meyerhardt JA, Wolpin BM, Fidias P, Zheng H, Florio S, Regan E, Fuchs CS (2011) A multicenter phase II trial of single-agent cetuximab in advanced esophageal and gastric adenocarcinoma. Ann Oncol 22:1367–1373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Cronin J, McAdam E, Danikas A, Tselepis C, Griffiths P, Baxter J, Thomas L, Manson J, Jenkins G (2011) Epidermal growth factor receptor (EGFR) is overexpressed in high-grade dysplasia and adenocarcinoma of the esophagus and may represent a biomarker of histological progression in Barrett’s esophagus (BE). Am J Gastroenterol 106:46–56

    Article  CAS  PubMed  Google Scholar 

  5. De Vita F, Orditura M, Martinelli E, Vecchione L, Innocenti R, Sileni VC, Pinto C, Di Maio M, Farella A, Troiani T, Morgillo F, Napolitano V, Ancona E, Di Martino N, Ruol A, Galizia G, Del Genio A, Ciardiello F (2011) A multicenter phase II study of induction chemotherapy with FOLFOX-4 and cetuximab followed by radiation and cetuximab in locally advanced oesophageal cancer. Br J Cancer 104:427–432

    Article  PubMed  PubMed Central  Google Scholar 

  6. Epperly MW, Guo H, Shen H, Niu Y, Zhang X, Jefferson M, Sikora CA, Greenberger JS (2004) Bone marrow origin of cells with capacity for homing and differentiation to esophageal squamous epithelium. Radiat Res 162:233–240

    Article  CAS  PubMed  Google Scholar 

  7. Farris 3rd AB, Demicco EG, Le LP, Finberg KE, Miller J, Mandal R, Fukuoka J, Cohen C, Gaissert HA, Zukerberg LR, Lauwers GY, Iafrate AJ, Mino-Kenudson M (2011) Clinicopathologic and molecular profiles of microsatellite unstable Barrett Esophagus-associated adenocarcinoma. Am J Surg Pathol 35:647–655

    Article  PubMed  Google Scholar 

  8. Fassan M, Volinia S, Palatini J, Pizzi M, Baffa R, De Bernard M, Battaglia G, Parente P, Croce CM, Zaninotto G, Ancona E, Rugge M (2011) MicroRNA expression profiling in human Barrett’s carcinogenesis. Int J Cancer 129:1661–1670

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Gatenby PA, Ramus JR, Caygill CP, Shepherd NA, Watson A (2008) Relevance of the detection of intestinal metaplasia in non-dysplastic columnar-lined oesophagus. Scand J Gastroenterol 43:524–530

    Article  PubMed  Google Scholar 

  10. Gillham CM, Reynolds J, Hollywood D (2007) Predicting the response of localised oesophageal cancer to neo-adjuvant chemoradiation. World J Surg Oncol 5:97

    Article  PubMed  PubMed Central  Google Scholar 

  11. Gyobu K, Yamashita S, Matsuda Y, Igaki H, Niwa T, Oka D, Kushima R, Osugi H, Lee S, Suehiro S, Ushijima T (2010) Identification and validation of DNA methylation markers to predict lymph node metastasis of esophageal squamous cell carcinomas. Ann Surg Oncol 18:1185–1194

    Article  PubMed  Google Scholar 

  12. Hamano R, Miyata H, Yamasaki M, Kurokawa Y, Hara J, Moon JH, Nakajima K, Takiguchi S, Fujiwara Y, Mori M, Doki Y (2011) Overexpression of miR-200c induces chemoresistance in esophageal cancers mediated through activation of the Akt signalling pathway. Clin Cancer Res 17:3029–3038

    Article  CAS  PubMed  Google Scholar 

  13. Hanawa M, Suzuki S, Dobashi Y, Yamane T, Kono K, Enomoto N, Ooi A (2006) EGFR protein overexpression and gene amplification in squamous cell carcinomas of the esophagus. Int J Cancer 118:1173–1180

    Article  CAS  PubMed  Google Scholar 

  14. Herrmann K, Walch A, Balluff B, Tänzer M, Höfler H, Krause BJ, Schwaiger M, Friess H, Schmid RM, Ebert MP (2009) Proteomic and metabolic prediction of response to therapy in gastrointestinal cancers. Nat Clin Pract Gastroenterol Hepatol 6:170–183

    Article  CAS  PubMed  Google Scholar 

  15. Hu N, Wang C, Hu Y, Yang HH, Giffen C, Tang ZZ, Han XY, Goldstein AM, Emmert-Buck MR, Buetow KH, Taylor PR, Lee MP (2005) Genome-wide association study in esophageal cancer using GeneChip mapping 10 K array. Cancer Res 65:2542–2546

    Article  CAS  PubMed  Google Scholar 

  16. Ito T, Sato F, Kan T, Cheng Y, David S, Agarwal R, Paun BC, Jin Z, Olaru AV, Hamilton JP, Selaru FM, Yang J, Matsumura N, Shimizu K, Abraham JM, Shimada Y, Mori Y, Meltzer SJ (2011) Polo-like kinase 1 regulates cell proliferation and is targeted by miR-593* in esophageal cancer. Int J Cancer 129:2134–2146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Jankowski JA, Wright NA, Meltzer SJ, Triadafilopoulos G, Geboes K, Casson AG, Kerr D, Young LS (1999) Molecular evolution of the metaplasia-dysplasia-adenocarcinoma sequence in the esophagus. Am J Pathol 154:965–973

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kaz AM, Wong CJ, Luo Y, Virgin JB, Washington MK, Willis JE, Leidner RS, Chak A, Grady WM (2011) DNA methylation profiling in Barrett's esophagus and esophageal adenocarcinoma reveals unique methylation signatures and molecular subclasses. Epigenetics 6:1403–1412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kim SM, Park YY, Park ES, Cho JY, Izzo JG, Zhang D, Kim SB, Lee JH, Bhutani MS, Swisher SG, Wu X, Coombes KR, Maru D, Wang KK, Buttar NS, Ajani JA, Lee JS (2010) Prognostic biomarkers for esophageal adenocarcinoma identified by analysis of tumor transcriptome. PloS One 5:15074

    Article  Google Scholar 

  20. Lagarde SM, ten Kate FJ, Richel DJ, Offerhaus GJ, van Lanschot JJ (2007) Molecular prognostic factors in adenocarcinoma of the esophagus and gastroesophageal junction. Ann Surg Oncol 14:977–991

    Article  CAS  PubMed  Google Scholar 

  21. Langer R, Ott K, Specht K, Becker K, Lordick F, Burian M, Herrmann K, Schrattenholz A, Cahill MA, Schwaiger M, Hofler H, Wester HJ (2008) Protein expression profiling in esophageal adenocarcinoma patients indicates association of heat-shock protein 27 expression and chemotherapy response. Clin Cancer Res 14:8279–8287

    Article  CAS  PubMed  Google Scholar 

  22. Langer R, Rauser S, Feith M, Nährig JM, Feuchtinger A, Friess H, Höfler H, Walch A (2011) Assessment of ErbB2 (Her2) in oesophageal adenocarcinomas: summary of a revised immunohistochemical evaluation system, bright field double in situ hybridisation and fluorescence in situ hybridisation. Mod Pathol 24:908–916

    Article  CAS  PubMed  Google Scholar 

  23. Leedham SJ, Preston SL, McDonald SA, Elia G, Bhandari P, Poller D, Harrison R, Novelli MR, Jankowski JA, Wright NA (2008) Individual crypt genetic heterogeneity and the origin of metaplastic glandular epithelium in human Barrett’s oesophagus. Gut 57:1041–1048

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Leidner RS, Ravi L, Leahy P, Chen Y, Bednarchik B, Streppel M, Canto M, Wang JS, Maitra A, Willis J, Markowitz SD, Barnholtz-Sloan J, Adams MD, Chak A, Guda K (2012) The microRNAs, MiR-31 and MiR-375, as candidate markers in Barrett's esophageal carcinogenesis. Genes Chromosomes Cancer 51:473–479

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Lennerz JK, Kwak EL, Ackerman A, Michael M, Fox SB, Bergethon K, Lauwers GY, Christensen JG, Wilner KD, Haber DA, Salgia R, Bang YJ, Clark JW, Solomon BJ, Iafrate AJ (2011) MET amplification identifies a small and aggressive subgroup of esophagogastric adenocarcinoma with evidence of responsiveness to crizotinib. J Clin Oncol 29:4803–4810

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Lima SC, Hernández-Vargas H, Simão T, Durand G, Kruel CD, Le Calvez-Kelm F, Ribeiro Pinto LF, Herceg Z (2011) Identification of a DNA methylome signature of esophageal squamous cell carcinoma and potential epigenetic biomarkers. Epigenetics 6:1217–1227

    Article  CAS  PubMed  Google Scholar 

  27. Lin DC, Du XL, Wang MR (2009) Protein alterations in ESCC and clinical implications: a review. Dis Esophagus 22:9–20

    Article  PubMed  Google Scholar 

  28. Lin DC, Zhang Y, Pan QJ, Yang H, Shi ZZ, Xie ZH, Wang BS, Hao JJ, Zhang TT, Xu X, Zhan QM, Wang MR (2011) PLK1 Is transcriptionally activated by NF-κB during cell detachment and enhances anoikis resistance through inhibiting β-catenin degradation in esophageal squamous cell carcinoma. Clin Cancer Res 17:4285–4295

    Article  CAS  PubMed  Google Scholar 

  29. Morales CP, Souza RF, Spechler SJ (2002) Hallmarks of cancer progression in Barrett’s oesophagus. Lancet 360:1587–1589

    Article  PubMed  Google Scholar 

  30. Moyes LH, Going JJ (2011) Still waiting for predictive biomarkers in Barrett's oesophagus. J Clin Pathol 64:742–750

    Article  CAS  PubMed  Google Scholar 

  31. Pande AU, Iyer RV, Rani A, Maddipatla S, Yang GY, Nwogu CE, Black JD, Levea CM, Javle MM (2007) Epidermal growth factor receptor-directed therapy in esophageal cancer. Oncology 73:281–289

    Article  CAS  PubMed  Google Scholar 

  32. Peng D, Sheta EA, Powell SM, Moskaluk CA, Washington K, Goldknopf IL, El-Rifai W (2008) Alterations in Barrett's-related adenocarcinomas: a proteomic approach. Int J Cancer 122:1303–1310

    Article  CAS  PubMed  Google Scholar 

  33. Peters CJ, Rees JR, Hardwick RH, Hardwick JS, Vowler SL, Ong CA, Zhang C, Save V, O’Donovan M, Rassl D, Alderson D, Caldas C, Fitzgerald RC (2010) Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Study Group. A 4-gene signature predicts survival of patients with resected adenocarcinoma of the esophagus, junction, and gastric cardia. Gastroenterology 139(15):1995–2004

    Article  CAS  PubMed  Google Scholar 

  34. Phillips BE, Tubbs RR, Rice TW, Rybicki LA, Plesec T, Rodriguez CP, Videtic GM, Saxton JP, Ives DI, Adelstein DJ (2012) Clinicopathologic features and treatment outcomes of patients with human epidermal growth factor receptor 2-positive adenocarcinoma of the esophagus and gastroesophageal junction. Dis Esophagus 2012 Jun 7: ([Epub ahead of print])

    Google Scholar 

  35. Reichelt U, Duesedau P, Tsourlakis MCh, Quaas A, Link BC, Schurr PG, Kaifi JT, Gros SJ, Yekebas EF, Marx A, Simon R, Izbicki JR, Sauter G (2007) Frequent homogeneous HER-2 amplification in primary and metastatic adenocarcinoma of the esophagus. Mod Pathol 20:120–129

    Article  CAS  PubMed  Google Scholar 

  36. Reid BJ, Prevo LJ, Galipeau PC, Sanchez CA, Longton G, Levine DS, Blount PL, Rabinovitch PS (2001) Predictors of progression in Barrett’s esophagus II: baseline 17p (p53) loss of heterozygosity identifies a patient subset at increased risk for neoplastic progression. Am J Gastroenterol 96:2839–2848

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Rugge M, Fassan M, Zaninotto G, Pizzi M, Giacomelli L, Battaglia G, Rizzetto C, Parente P, Ancona E (2010) Aurora kinase A in Barrett’s carcinogenesis. Hum Pathol 41:1380–1386

    Article  CAS  PubMed  Google Scholar 

  38. Rumiato E, Pasello G, Montagna M, Scaini MC, De Salvo GL, Parenti A, Cagol M, Ruol A, Ancona E, Amadori A, Saggioro D (2011) DNA copy number profile discriminates between esophageal adenocarcinoma and squamous cell carcinoma and represents an independent prognostic parameter in esophageal adenocarcinoma. Cancer Lett 310:84–93

    Article  CAS  PubMed  Google Scholar 

  39. Safran H, Dipetrillo T, Akerman P, Ng T, Evans D, Steinhoff M, Benton D, Purviance J, Goldstein L, Tantravahi U, Kennedy T (2007) Phase I/II study of trastuzumab, paclitaxel, cisplatin and radiation for locally advanced, HER2 overexpressing, esophageal adenocarcinoma. Int J Rad Oncol Biol Phys 67:405–409

    Article  CAS  Google Scholar 

  40. Shi ZZ, Liang JW, Zhan T, Wang BS, Lin DC, Liu SG, Hao JJ, Yang H, Zhang Y, Zhan QM, Zhang KT, Wang MR (2011) Genomic alterations with impact on survival in esophageal squamous cell carcinoma identified by array comparative genomic hybridization. Genes Chromosomes Cancer 50:518–526

    Article  CAS  PubMed  Google Scholar 

  41. Song JH, Meltzer SJ (2012) MicroRNAs in pathogenesis, diagnosis, and treatment of gastroesophageal cancers. Gastroenterology 143:35–47

    Article  CAS  PubMed  Google Scholar 

  42. Souza RF (2010) The molecular basis of carcinogenesis in Barrett’s esophagus. J Gastrointest Surg 14:937–940

    Article  PubMed  PubMed Central  Google Scholar 

  43. Su H, Hu N, Yang HH, Wang C, Takikita M, Wang QH, Giffen C, Clifford R, Hewitt SM, Shou JZ, Goldstein AM, Lee MP, Taylor PR (2011) Global gene expression profiling and validation in esophageal squamous cell carcinoma and its association with clinical phenotypes. Clin Cancer Res 17:2955–2966

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Sugimachi K, Sumiyoshi K, Nozoe T, Yasuda M, Watanabe M, Kitamura K, Tsutsui S, Mori M, Kuwano H (1995) Carcinogenesis and histogenesis of esophageal carcinoma. Cancer 75:1440–1445

    Article  CAS  PubMed  Google Scholar 

  45. Tafe LJ, Janjigian YY, Zaidinski M, Hedvat CV, Hameed MR, Tang LH, Hicks JB, Shah MA, Barbashina V (2011) Human epidermal growth factor receptor 2 testing in gastroesophageal cancer: correlation between immunohistochemistry and fluorescence in situ hybridization. Arch Pathol Lab Med 135:1460–1465

    Article  CAS  PubMed  Google Scholar 

  46. Takubo K, Aida J, Naomoto Y, Sawabe M, Arai T, Shiraishi H, Matsuura M, Ell C, May A, Pech O, Stolte M, Vieth M (2009) Cardiac rather than intestinal-type background in endoscopic resection specimens of minute Barrett adenocarcinoma. Hum Pathol 40:65–74

    Article  PubMed  Google Scholar 

  47. Tew WP, Kelsen DP, Ilson DH (2005) Targeted therapies for esophageal cancer. Oncologist 10:590–601

    Article  CAS  PubMed  Google Scholar 

  48. Thompson SK, Sullivan TR, Davies R, Ruszkiewicz AR (2011) Her-2/neu gene amplification in esophageal adenocarcinoma and its influence on survival. Ann Surg Oncol 18:2010–2017

    Article  PubMed  Google Scholar 

  49. Vallböhmer D, Brabender J, Metzger R, Hölscher AH (2010) Genetics in the pathogenesis of esophageal cancer: possible predictive and prognostic factor. J Gastrointest Surg 14(1):75–80

    Article  Google Scholar 

  50. Vega KJ, May R, Sureban SM, Lightfoot SA, Qu D, Reed A, Weygant N, Ramanujam R, Souza R, Madhoun M, Whorton J, Anant S, Meltzer S, Houchen CW (2012) Identification of the putative intestinal stem cell marker DCAMKL-1 in Barrett's Esophagus and Esophageal Adenocarcinoma. J Gastroenterol Hepatol 27:773–780

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Walch A, Specht K, Bink K, Zitzelsberger H, Braselmann H, Bauer M, Aubele M, Stein H, Siewert JR, Höfler H, Werner M (2001) Her-2/neu gene amplification, elevated mRNA expression, and protein overexpression in the metaplasia-dysplasia-adenocarcinoma sequence of Barrett’s esophagus. Lab Invest 81:791–801

    Article  CAS  PubMed  Google Scholar 

  52. Werner M, Lassmann S (2011) Intraepithelial neoplasia of Barrett's esophagus: prognosis of potential malignancy. Pathologe 32(2):197–201

    Article  PubMed  Google Scholar 

  53. Wiech T, Nikolopoulos E, Weis R, Langer R, Bartholomé K, Timmer J, Walch AK, Höfler H, Werner M (2009) Genome-wide analysis of genetic alterations in Barrett’s adenocarcinoma using single nucleotide polymorphism arrays. Lab Invest 89:385–397

    Article  CAS  PubMed  Google Scholar 

  54. Zhang HY, Spechler SJ, Souza RF (2008) Esophageal adenocarcinoma arising in Barrett esophagus. Cancer Lett 275:170–177

    Article  PubMed  PubMed Central  Google Scholar 

  55. Zhang J, Wang K, Zhang J, Liu SS, Dai L, Zhang JY (2011) Using proteomic approach to identify tumor-associated proteins as biomarkers in human esophageal squamous cell carcinoma. J Proteome Res 10:2863–2872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Zhang Y, Du XL, Wang CJ, Lin DC, Ruan X, Feng YB, Huo YQ, Peng HY, Cui JL, Zhang TT, Wang YQ, Zhang H, Zhan QM, Wang MR (2012) Reciprocal activation between PLK1 and Stat3 contributes to survival and proliferation of esophageal cancer cells. Gastroenterology 142(3):521–530

    Article  CAS  PubMed  Google Scholar 

  57. Zhao JS, Li WJ, Ge D, Zhang PJ, Li JJ, Lu CL, Ji XD, Guan DX, Gao H, Xu LY, Li EM, Soukiasian H, Koeffler HP, Wang XF, Xie D (2011) Tumor initiating cells in esophageal squamous cell carcinomas express high levels of CD44. PLoS One 6:21419

    Article  Google Scholar 

  58. Zhu X, Ding M, Yu ML, Feng MX, Tan LJ, Zhao FK (2010) Identification of galectin-7 as a potential biomarker for esophageal squamous cell carcinoma by proteomic analysis. BMC Cancer 10:290

    Article  PubMed  PubMed Central  Google Scholar 

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Author notes

  1. Silke Laßmann Prof. Dr. & Martin Werner Prof. Dr. med.

    Present address: Institut für Pathologie, Ludwig Aschoff-Haus, Abt. Allgemeine Pathologie und Pathologische Anatomie, Universitätsklinikum Freiburg, Breisacherstr. 115a, 79106, Freiburg, Deutschland

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    1. Silke Laßmann Prof. Dr.
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    2. Martin Werner Prof. Dr. med.
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    Correspondence to Silke Laßmann Prof. Dr. .

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    Editors and Affiliations

    1. Institut für Pathologie, Klinikum Kulmbach, Kulmbach, Germany

      Manfred Stolte

    2. Institut für Pathologie Nordhessen, Kassel, Germany

      Josef Rüschoff

    3. Konsultationszentrum für Pankreas- und, Technische Universität München Klinikum rechts der Isar, München, Germany

      Günter Klöppel

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    Laßmann, S., Werner, M. (2013). Molekularpathologie der malignen Tumoren des Ösophagus. In: Stolte, M., Rüschoff, J., Klöppel, G. (eds) Pathologie. Pathologie. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-02322-4_4

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    • DOI: https://doi.org/10.1007/978-3-642-02322-4_4

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