Skip to main content
SpringerLink
Log in

Diagnostik des Lungenkarzinoms

Gewebegewinnung in Zeiten molekularer Methoden

Diagnostics of lung cancer

Tissue harvesting in the era of molecular diagnostics

  • Leitthema
  • Published:
Der Pneumologe Aims and scope

Zusammenfassung

Hintergrund

Mit der histologischen Differenzierung und Entdeckung neuer onkogener Treibermutationen bei Adenokarzinomen und mit der Einführung zielgerichteter Therapien lässt sich mit einer personalisierten Medizin die Prognose bestimmter Patientenkollektive signifikant verbessern.

Ziel der Arbeit

Minimal-invasive, endoskopische Methoden stehen neben chirurgischen Verfahren zur Verfügung, um histologisches und zytologisches Material für die molekulare Diagnostik zu gewinnen. Die verschiedenen diagnostischen Optionen mit Vor- und Nachteilen werden beschrieben.

Material und Methoden

Aktuelle Literaturrecherche bei PubMed.

Ergebnisse

Eine molekulare Diagnostik sollte bei jedem Patienten aus klinisch praktikablen Gründen aus möglichst kleinen Biopsien durchgeführt werden können. Endoskopische transbronchiale Nadelaspirationen (TBNA) weisen eine hohe Sensitivität auf und stellen die Diagnostik der ersten Wahl dar. Bei radiologischem Verdacht einer Lymphknotenmetastasierung und zytologisch negativem Befund ist eine chirurgische Evaluation weiterhin notwendig.

Diskussion

Ziel wird es sein, weitere molekulare Alterationen zu finden, die eine zielgerichtete Therapie möglich machen und die als prognostische Biomarker oder Prädiktoren für das Therapieansprechen dienen können. Die Erforschung komplett nichtinvasiver Verfahren wie die Analyse zirkulierender Tumorzellen geht weiter.

Abstract

Background

The prognosis of specific subgroups of patients has been significantly improved by a personalized medicine due to histological differentiation, discovery of new oncogene driver mutations in adenocarcinomas and the introduction of targeted therapies.

Objective

Minimally invasive endoscopic methods as well as surgical procedures are available for obtaining histological and cytological material for molecular diagnostics. The various diagnostic options with their advantages and disadvantages are described.

Material and methods

A literature search was carried out in PubMed.

Results

In every patient it should be possible for clinically practical reasons to perform molecular diagnostic investigations on biopsies, which are as small as possible. Endoscopic transbronchial needle aspiration (TBNA) has a high sensitivity and represents the diagnostic method of choice. If radiologically suspicious mediastinal lymph nodes are present and the cytological result is negative, surgical evaluation is still necessary.

Discussion

In the future the aim will be to find further molecular alterations that make a targeted therapy possible and which can be used as prognostic biomarkers or to predict therapy response. Research into entirely noninvasive methods, such as analysis of circulating tumor cells is ongoing.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2
Abb. 3
Abb. 4
Abb. 5
Abb. 6

Literatur

  1. Block MI (2010) Transition from mediastinoscopy to endoscopic ultrasound for lung cancer staging. Ann Thorac Surg 89(3):885–890

    Article  PubMed  Google Scholar 

  2. Casadio C, Guarize J, Donghi S, Tonno C Di, Fumagalli C, Vacirca D, Dell’Orto P, Marinis F De, Spaggiari L, Viale G, Barberis M (2015) Molecular testing for targeted therapy in advanced non-small cell lung cancer: suitability of endobronchial ultrasound transbronchial needle aspiration. Am J Clin Pathol 144(4):629–634

    Article  PubMed  Google Scholar 

  3. Cheng H, Xu X, Costa DB, Powell CA, Halmos B (2010) Molecular testing in lung cancer: The time is now. Curr Oncol Rep 12(5):335–348

    Article  CAS  PubMed  Google Scholar 

  4. Crisci R, Cesare E Di, Lupattelli L, Coloni GF (1997) MR study of N2 disease in lung cancer: contrast-enhanced method using gadolinium-DTPA. Eur J Cardiothorac Surg 11(2):214–217

    Article  CAS  PubMed  Google Scholar 

  5. Dietel M, Bubendorf L, Dingemans AC, Dooms C, Elmberger G, García RC, Kerr KM, Lim E, López-Ríos F, Thunnissen E, Van Schil PE, Laffert M von (2015) Diagnostic procedures for non-small-cell lung cancer (NSCLC): Recommendations of the European Expert Group. Thorax (Epub ahead of print)

  6. Dooms C, Tournoy KG, Schuurbiers O (2015) Endosonography for mediastinal nodal staging of clinical N1 non-small cell lung cancer: A prospective multicenter study. Chest 147:209–215

    Article  PubMed  Google Scholar 

  7. Eberhardt R, Kahn N, Gompelmann D (2010) LungPoint – a new approach to peripheral lesions. J Thorac Oncol 5:1559–1563

    Article  PubMed  Google Scholar 

  8. Eberhardt R, Anantham D, Herth F, Feller-Kopman D, Ernst A (2007) Electromagnetic navigation diagnostic bronchoscopy in peripheral lung lesions. Chest 131:1800–1805

    Article  PubMed  Google Scholar 

  9. Herth FJ, Krasnik M, Kahn N, Eberhardt R, Ernst A (2010) Combined endoscopic-endobronchial ultrasound-guided fine-needle aspiration of mediastinal lymph nodes through a single bronchoscope in 150 patients with suspected lung cancer. Chest 138(4):790–794

    Article  PubMed  Google Scholar 

  10. Herth FJ, Eberhardt R, Vilmann P, Krasnik M, Ernst A (2006) Real-time endobronchial ultrasound guided transbronchial needle aspiration for sampling mediastinal lymph nodes. Thorax 61(9):795–798

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Herth FJ, Eberhardt R, Krasnik M (2008) Endobronchial ultrasound- guided transbronchial needle aspiration of lymph nodes in the radiologically and positron emission tomography-normal mediastinum in patients with lung cancer. Chest 133:887–891

    Article  PubMed  Google Scholar 

  12. Hetzel J, Eberhardt R, Herth FJ (2012) Cryobiopsy increases the diagnostic yield of endobronchial biopsy: A multicentre trial. Eur Respir J 39(3):685–690

    Article  CAS  PubMed  Google Scholar 

  13. Ma BB, Hui EP, Mok TS (2010) Population-based differences in treatment outcome following anticancer drug therapies. Lancet Oncol 11(1):75–84

    Article  PubMed  Google Scholar 

  14. Maheswaran S, Sequist LV, Nagrath S (2008) Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med 359(4):366–377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Malvezzi M, Bertuccio P, Rosso T (2015) European cancer mortality predictions for the year 2015: does lung cancer have the highest death rate in EU women? Ann Oncol 26(4):779–786

    Article  CAS  PubMed  Google Scholar 

  16. Nakamura H, Aute I, Kawasaki N, Taguchi M, Ohira T, Kato H (2005) Quantitative detection of lung cancer cells by fluorescence in situ hybridization: comparison with conventional cytology. Chest 128(2):906–911

    Article  PubMed  Google Scholar 

  17. Newman AM, Bratman SV, To J (2014) An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage. Nat Med 20(5):548–554

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ohnishi R, Yasuda I, Kato T (2011) Combined endobronchial and endoscopic ultrasound-guided fine needle aspiration for mediastinal nodal staging of lung cancer. Endoscopy 43:1082–1089

    Article  CAS  PubMed  Google Scholar 

  19. Ost DE, Ernst A, Lei X, Kovitz KL, Benzaquen S, Diaz-Mendoza S (2015) Diagnostic yield and complications of bronchoscopy for peripheral lung lesions: Results of the AQuIRE registry. Am J Respir Crit Care Med (Epub ahead of print)

  20. Pao W, Girard N (2011) New driver mutations in non-small-cell lung cancer. Lancet Oncol 12(2):175–180

    Article  CAS  PubMed  Google Scholar 

  21. Planchard D, Mazieres J, Riely GJ (2013) Interim results of Phase II study BRF113928 of dabrafenib in BRAF V600E mutation-positive non-small cell lung cancer (NSCLC) patients American Society Clinical Onology Annual Meeting, Chicago, 31 May–4 June 2013. (Abstract8009)

    Google Scholar 

  22. Reya T, Morrison SJ, Clarke MF, Weissman IL (2001) Stem cells, cancer, and cancer stem cells. Nature 414:105–111

    Article  CAS  PubMed  Google Scholar 

  23. Rodríguez CF de, Rey A, Caminero J (1995) Transbronchial fine needle aspiration in clinical practice. Cytopathology 6(1):22–29

    Article  Google Scholar 

  24. Rosell R, Carcereny E, Gervais R (2012) Erlotinib versus standard chemotherapy as first-line treatment for european patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): A multicentre, open-label, randomised phase 3 trial. Lancet Oncol 13(3):239–246

    Article  CAS  PubMed  Google Scholar 

  25. Sayar A, Citak N, Metin M (2011) Comparison of videoassisted mediastinoscopy and video-assisted mediastinoscopic lymphadenectomy for lung cancer. Gen Thorac Cardiovasc Surg 59(12):793–798

    Article  PubMed  Google Scholar 

  26. Schenk DA, Bower JH, Bryan CL (1986) Transbronchial needle aspiration staging of bronchogenic carcinoma. Am Rev Respir Dis 134(1):146–148

    CAS  PubMed  Google Scholar 

  27. Sebastián-Quetglás F, Molins L, Baldó X, Buitrago J, Vidal G (2003) Spanish video-assisted thoracic surgery study group. Clinical value of video-assisted thoracoscopy for preoperative staging of non-small cell lung cancer. A prospective study of 105 patients. Lung Cancer 42(3):297–301

    Article  PubMed  Google Scholar 

  28. Sequist LV, Heist RS, Shaw AT (2011) Implementing multiplexed genotyping of non-small-cell lung cancers into routine clinical practice. Ann Oncol 22(12):2616–2624

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Sequist LV, Yang JC, Yamamoto N (2012) Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol 27:3327–3334

    Google Scholar 

  30. Serra M, Cirera L (2006) Routine positron tomography (PET) and selective mediastinoscopy is as good as routine mediastinoscopy to rule out N2 disease in non-small cell lung cancer (NSCLC). J Clin Oncol 24:371S

    Google Scholar 

  31. Shaw AT, Kim DW, Nakagawa K (2013) Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med 368(25):2385–2394

    Article  CAS  PubMed  Google Scholar 

  32. Silvestri GA, Gonzalez AV, Jantz MA, Margolis ML, Gould MK, Tanoue LT, Harris LJ, Detterbeck FC (2013) Methods for staging non-small cell lung cancer: Diagnosis and management of lung cancer. Chest 143:e211–e250 (3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines)

    Article  Google Scholar 

  33. Sorger H, Hofstad EF, Amundsen T, Lango T, Leira HO (2015) A novel platform for eletromegnetiv navigated ultrasaound bronchoskopy (EBUS). Int J Comput Assist Radiol Surg (Epub ahead of print)

  34. Steinfort DP, Khor YH, Manser RL (2011) Radial probe endobronchial ultrasound for the diagnosis of peripheral lung cancer: Systematic review and meta-analysis. Eur Respir J 37:902–910

    Article  CAS  PubMed  Google Scholar 

  35. Steinfort DP, Bonney A, See K, Irving LB (2015) Sequential multimodality bronchoscopic investigation of peripheral pulmonary lesions. Eur Respir J. doi:10.1183/13993003.00786-2015

    Google Scholar 

  36. The American Thoracic Society and The European Respiratory Society (1997) Pretreatment evaluation of non-small-cell lung cancer. Am J Respir Crit Care Med 156(1):320–332

    Article  Google Scholar 

  37. Heijden EH Van der, Casal RF, Trisolini R, Steinfort DP, Hwangbo B, Nakajima T, Guldhammer-Skov B (2014) Guideline fort he acquisition and preparation of conventionel and endobronchial ultrasound-guided transbronchial needle aspiration specimens fort he diagnosis and molecular testing of patients with known or suspected lung cancer. Respiration 88(6):500–517

    PubMed  Google Scholar 

  38. Wang Memoli JS, Nietert PJ, Silvestri GA (2012) Meta-analysis of guided bronchoskopy fot the evaluation oft he pulmonary nodule. Chest 142(2):385–393

    Article  PubMed  Google Scholar 

  39. Yang B, Li F, Shi W (2014) Endobronchial ultrasoundguided transbronchial needle biopsy for the diagnosis of intrathoracic lymph node metastases from extrathoracic malignancies: A meta-analysis and systematic review. Respirology 19:834–841

    Article  PubMed  Google Scholar 

Download references

Danksagung

Wir danken den Herren Prof. Dr. R. Eberhardt, Dr. Gompelmann und Prof. Dr. C.P. Heußel, Heidelberg, für die Überlassung der Abbildungen 1–5.

Author information

Authors and Affiliations

  1. Thoraxklinik am Universitätsklinikum Heidelberg, Röntgenstr. 1, 69126, Heidelberg, Deutschland

    P. Kaukel & F. J. F. Herth

Authors
  1. P. Kaukel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. J. F. Herth
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P. Kaukel.

Ethics declarations

Interessenkonflikt

P. Kaukel und F.J.F. Herth geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

Additional information

Redaktion

B. Jany, Würzburg

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kaukel, P., Herth, F.J.F. Diagnostik des Lungenkarzinoms. Pneumologe 13, 223–232 (2016). https://doi.org/10.1007/s10405-016-0045-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10405-016-0045-2

Schlüsselwörter

Keywords

Search

Navigation