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Translationale Forschung und Diagnostik beim Lungenkarzinom

Translational research and diagnostics in lung cancer

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Zusammenfassung

Malignome der Lunge sind die häufigste tumorassoziierte Todesursache weltweit. Lange Zeit wurden Lungenkarzinome lediglich in kleinzellige („small cell lung cancer“, SCLC) und nichtkleinzellige Karzinome („non-small cell lung cancer“, NSCLC) unterteilt, wobei hier Adenokarzinome und Plattenepithelkarzinome die häufigsten Entitäten darstellen. Diese grobe Einteilung gilt jedoch als überholt, da durch die molekulare Aufschlüsselung genetischer Aberrationen ständig neue Subkategorien innerhalb bisher histologisch definierter Tumorentitäten entstehen. Durch diese detailliertere Beschreibung pulmonaler Malignome entstehen neue Kategorien mit spezifischer Tumordiagnose, individueller Prognose sowie rationalen Therapiemöglichkeiten. Bislang galten die malignen Lymphome als Prototyp für eine sinnvolle Subkategorisierung einer Tumorentität unter Berücksichtigung pathognomonisch relevanter molekularer Veränderungen. Mittlerweile sind auch bei den Lungenkarzinomen molekulare Charakteristika integraler Bestandteil der Patientenversorgung. Darüber hinaus können auch Erkenntnisse aus der molekularen Kategorisierung der Lungenkarzinome als Modell für die Charakterisierung von Tumoren anderer Organsysteme gesehen werden.

Abstract

Lung cancer is the most common malignant disease leading to death worldwide. Histologically, it is broadly subcategorized into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), with the latter mainly consisting of the major entities adenocarcinoma and squamous cell carcinoma. However, molecular profiling of various lung cancer entities has revealed major molecular differences within distinct histological tumor entities, resulting in the integration of molecular alterations in the subclassification of lung cancers. These findings can only estimate the genetic complexity of lung tumors. Large scale molecular profiling has the potential to identify novel diagnostic, prognostic and predictive markers as well as therapeutic targets. Importantly, this recently arising categorization of lung carcinomas can be regarded as an example for the characterization of malignomas of other organ systems. The pioneer model for this molecular subcategorization is the classification of malignant lymphomas.

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Literatur

  1. Lynch TJ, Bell DW, Sordella R et al (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 350:2129–2139

    Article  PubMed  CAS  Google Scholar 

  2. Weinstein IB, Joe AK (2006) Mechanisms of disease: oncogene addiction: a rationale for molecular targeting in cancer therapy. Nat Clin Pract Oncol 3:448–457

    Article  PubMed  CAS  Google Scholar 

  3. Pao W, Miller VA, Kris MG (2004) ‚Targeting‘ the epidermal growth factor receptor tyrosine kinase with gefitinib (Iressa) in non-small cell lung cancer (NSCLC). Semin Cancer Biol 14:33–40

    Article  PubMed  CAS  Google Scholar 

  4. Hirsch FR, Varella-Garcia M, Bunn PA Jr et al (2003) Epidermal growth factor receptor in non-small-cell lung carcinomas: correlation between gene copy number and protein expression and impact on prognosis. J Clin Oncol 21:3798–3807

    Article  PubMed  CAS  Google Scholar 

  5. Reinmuth N, Brandt B, Kunze WP et al (2000) Ploidy, expression of erbB1, erbB2, P53 and amplification of erbB1, erbB2 and erbB3 in non-small cell lung cancer. Eur Respir J 16:991–996

    Article  PubMed  CAS  Google Scholar 

  6. Ohsaki Y, Tanno S, Fujita Y et al (2000) Epidermal growth factor receptor expression correlates with poor prognosis in non-small cell lung cancer patients with p53 overexpression. Oncol Rep 7:603–607

    PubMed  CAS  Google Scholar 

  7. Volm M, Rittgen W, Drings P (1998) Prognostic value of ERBB-1, VEGF, cyclin A, FOS, JUN and MYC in patients with squamous cell lung carcinomas. Br J Cancer 77:663–669

    Article  PubMed  CAS  Google Scholar 

  8. Rusch V, Klimstra D, Venkatraman E et al (1997) Overexpression of the epidermal growth factor receptor and its ligand transforming growth factor alpha is frequent in resectable non-small cell lung cancer but does not predict tumor progression. Clin Cancer Res 3:515–522

    PubMed  CAS  Google Scholar 

  9. Pfeiffer P, Clausen PP, Andersen K et al (1996) Lack of prognostic significance of epidermal growth factor receptor and the oncoprotein p185HER-2 in patients with systemically untreated non-small-cell lung cancer: an immunohistochemical study on cryosections. Br J Cancer 74:86–91

    Article  PubMed  CAS  Google Scholar 

  10. Soda M, Choi YL, Enomoto M et al (2007) Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 448:561–566

    Article  PubMed  CAS  Google Scholar 

  11. Inamura K, Takeuchi K, Togashi Y et al (2008) EML4-ALK fusion is linked to histological characteristics in a subset of lung cancers. J Thorac Oncol 3:13–17

    Article  PubMed  Google Scholar 

  12. Perner S, Wagner PL, Demichelis F et al (2008) EML4-ALK fusion lung cancer: a rare acquired event. Neoplasia 10:298–302

    PubMed  CAS  Google Scholar 

  13. Kwak EL, Bang YJ, Camidge DR et al (2010) Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med 363:1693–1703

    Article  PubMed  CAS  Google Scholar 

  14. Weir BA, Woo MS, Getz G et al (2007) Characterizing the cancer genome in lung adenocarcinoma. Nature 450:893–898

    Article  PubMed  CAS  Google Scholar 

  15. Perner S, Wagner PL, Soltermann A et al (2009) TTF1 expression in non-small cell lung carcinoma: association with TTF1 gene amplification and improved survival. J Pathol 217:65–72

    Article  PubMed  CAS  Google Scholar 

  16. Bass AJ, Watanabe H, Mermel CH et al (2009) SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas. Nat Genet 41:1238–1242

    Article  PubMed  CAS  Google Scholar 

  17. Wilbertz T, Wagner P, Petersen K et al (2011) SOX2 gene amplification and protein overexpression are associated with better outcome in squamous cell lung cancer. Mod Pathol 24:944–953

    Article  PubMed  CAS  Google Scholar 

  18. Neumann J, Bahr F, Horst D et al (2011) SOX2 expression correlates with lymph-node metastases and distant spread in right-sided colon cancer. BMC Cancer 11:518

    Article  PubMed  Google Scholar 

  19. Du L, Yang Y, Xiao X et al (2011) Sox2 nuclear expression is closely associated with poor prognosis in patients with histologically node-negative oral tongue squamous cell carcinoma. Oral Oncol 47:709–713

    Article  PubMed  CAS  Google Scholar 

  20. Weiss J, Sos ML, Seidel D et al (2010) Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer. Sci Transl Med 2:62ra93

    Article  PubMed  CAS  Google Scholar 

  21. Goeke F, Franzen A, Menon R et al (2012) Rationale for treatment of metastatic squamous cell carcinoma of the lung using FGFR Inhibitors. Chest

  22. Freier K, Schwaenen C, Sticht C et al (2007) Recurrent FGFR1 amplification and high FGFR1 protein expression in oral squamous cell carcinoma (OSCC). Oral Oncol 43:60–66

    Article  PubMed  CAS  Google Scholar 

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  1. Abteilung für Prostatatkarzinom-Forschung, Institut für Pathologie, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Deutschland

    F. Göke &  S. Perner

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  1. F. Göke
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  2. S. Perner
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Correspondence to S. Perner.

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Göke, F., Perner, S. Translationale Forschung und Diagnostik beim Lungenkarzinom. Pathologe 33 (Suppl 2), 269–272 (2012). https://doi.org/10.1007/s00292-012-1664-y

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  • DOI: https://doi.org/10.1007/s00292-012-1664-y

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