Skip to main content
SpringerLink
Log in

Nichtkleinzelliges Lungenkarzinom – Pathologie und Biologie

Non-small cell lung cancer—pathology and biology

  • Leitthema
  • Published:
Der Onkologe Aims and scope

Zusammenfassung

Hintergrund

Nichtkleinzellige Lungenkarzinome (NSCLC) machen ca. 75 % der malignen epithelialen Lungentumoren aus. In den vergangenen Jahren konnten profunde Erkenntnisse über molekulare Mechanismen der Krebsentstehung der Lunge gewonnen werden und in der Folge zielgerichtete Substanzen („targeted drugs“) und immuntherapeutisch wirksame Medikamente entwickelt werden. Diese Fortschritte haben den Ablauf der pathologischen Diagnostik maßgeblich beeinflusst.

Ziel

Der vorliegende Artikel soll einen Überblick über die häufigsten histologischen Subtypen der NSCLC, ihre morphologischen, immunhistochemischen und molekularpathologischen Charakteristika geben.

Material und Methoden

Eine selektive Literaturrecherche der Datenbank Pubmed wurde durchgeführt.

Ergebnisse und Diskussion

Adenokarzinome, Plattenepithelkarzinome und großzellige Karzinome sind die häufigsten histologischen Subtypen. Durch die in der pathologischen Routine verfügbaren Zusatzuntersuchungen lassen sich in der Regel auch gering differenzierte Tumoren gut zuordnen. NSCLC zeigen eine Reihe genetischer Veränderungen, therapeutisch nutzbar sind Alterationen von EGFR, MET, ALK1 und ROS1.

Abstract

Background

Non-small cell lung cancer (NSCLC) accounts for ca. 75% of malignant epithelial neoplasms of the lungs. In recent years profound insight has been gained regarding the molecular mechanisms of lung carcinogenesis and subsequently new targeted therapies as well as immunotherapies have been developed. These advances have had a significant impact on routine diagnostics in pathology.

Objective

The article aims to give an overview of the most common histological subtypes of NSCLC as well as the morphological, immunohistochemical and molecular characteristics.

Material and methods

Selective search of the PubMed database.

Results and discussion

Adenocarcinomas, squamous cell carcinomas and large cell carcinomas are the most common histological subtypes. With the ancillary methods available in routine pathology even poorly differentiated tumors can be assigned to these entities. The NSCLC show numerous genetic changes of which alterations of EGFR, MET, ALK1 and ROS1 are target structures for personalized therapy.

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

Literatur

  1. Aredo JV, Padda SK (2018) Management of KRAS-mutant non-small cell lung cancer in the era of precision medicine. Curr Treat Options Oncol 19:43

    Article  Google Scholar 

  2. Barbareschi M, Cantaloni C, Del Vescovo V et al (2011) Heterogeneity of large cell carcinoma of the lung: an immunophenotypic and miRNA-based analysis. Am J Clin Pathol 136:773–782

    Article  Google Scholar 

  3. Bergethon K, Shaw AT, Ou SH et al (2012) ROS1 rearrangements define a unique molecular class of lung cancers. J Clin Oncol 30:863–870

    Article  CAS  Google Scholar 

  4. Boland JM, Froemming AT, Wampfler JA et al (2016) Adenocarcinoma in situ, minimally invasive adenocarcinoma, and invasive pulmonary adenocarcinoma--analysis of interobserver agreement, survival, radiographic characteristics, and gross pathology in 296 nodules. Hum Pathol 51:41–50

    Article  Google Scholar 

  5. Bubendorf L, Buttner R, Al-Dayel F et al (2016) Testing for ROS1 in non-small cell lung cancer: a review with recommendations. Virchows Arch 469:489–503

    Article  CAS  Google Scholar 

  6. Camidge DR, Kono SA, Flacco A et al (2010) Optimizing the detection of lung cancer patients harboring anaplastic lymphoma kinase (ALK) gene rearrangements potentially suitable for ALK inhibitor treatment. Clin Cancer Res 16:5581–5590

    Article  CAS  Google Scholar 

  7. Cancer Genome Atlas Research Network (2012) Comprehensive genomic characterization of squamous cell lung cancers. Nature 489:519–525

    Article  Google Scholar 

  8. Clinical Lung Cancer Genome Project, Network Genomic Medicine (2013) A genomics-based classification of human lung tumors. Sci Transl Med 5:209ra153

    Google Scholar 

  9. Davies KD, Doebele RC (2013) Molecular pathways: ROS1 fusion proteins in cancer. Clin Cancer Res 19:4040–4045

    Article  CAS  Google Scholar 

  10. Dearden S, Stevens J, Wu YL et al (2013) Mutation incidence and coincidence in non small-cell lung cancer: meta-analyses by ethnicity and histology (mutMap). Ann Oncol 24:2371–2376

    Article  CAS  Google Scholar 

  11. Dong H, Strome SE, Salomao DR et al (2002) Tumor-associated B7-H1 promotes T‑cell apoptosis: a potential mechanism of immune evasion. Nat Med 8:793–800

    Article  CAS  Google Scholar 

  12. Frampton GM, Ali SM, Rosenzweig M et al (2015) Activation of MET via diverse exon 14 splicing alterations occurs in multiple tumor types and confers clinical sensitivity to MET inhibitors. Cancer Discov 5:850–859

    Article  CAS  Google Scholar 

  13. Freeman GJ, Long AJ, Iwai Y et al (2000) Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 192:1027–1034

    Article  CAS  Google Scholar 

  14. Gainor JF, Shaw AT (2013) Novel targets in non-small cell lung cancer: ROS1 and RET fusions. Oncologist 18:865–875

    Article  CAS  Google Scholar 

  15. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674

    Article  CAS  Google Scholar 

  16. Joshi A, Zanwar S, Noronha V et al (2017) EGFR mutation in squamous cell carcinoma of the lung: does it carry the same connotation as in adenocarcinomas? Onco Targets Ther 10:1859–1863

    Article  CAS  Google Scholar 

  17. Jucker M, Gunther A, Gradl G et al (1994) The Met/hepatocyte growth factor receptor (HGFR) gene is overexpressed in some cases of human leukemia and lymphoma. Leuk Res 18:7–16

    Article  CAS  Google Scholar 

  18. Lewis DR, Check DP, Caporaso NE et al (2014) US lung cancer trends by histologic type. Cancer 120:2883–2892

    Article  Google Scholar 

  19. Mcleer-Florin A, Moro-Sibilot D, Melis A et al (2012) Dual IHC and FISH testing for ALK gene rearrangement in lung adenocarcinomas in a routine practice: a French study. J Thorac Oncol 7:348–354

    Article  Google Scholar 

  20. Park S, Choi YL, Sung CO et al (2012) High MET copy number and MET overexpression: poor outcome in non-small cell lung cancer patients. Histol Histopathol 27:197–207

    PubMed  Google Scholar 

  21. Rekhtman N, Tafe LJ, Chaft JE et al (2013) Distinct profile of driver mutations and clinical features in immunomarker-defined subsets of pulmonary large-cell carcinoma. Mod Pathol 26:511–522

    Article  CAS  Google Scholar 

  22. Reungwetwattana T, Liang Y, Zhu V et al (2017) The race to target MET exon 14 skipping alterations in non-small cell lung cancer: the why, the how, the who, the unknown, and the inevitable. Lung Cancer 103:27–37

    Article  Google Scholar 

  23. Rikova K, Guo A, Zeng Q et al (2007) Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell 131:1190–1203

    Article  CAS  Google Scholar 

  24. Sasaki T, Rodig SJ, Chirieac LR et al (2010) The biology and treatment of EML4-ALK non-small cell lung cancer. Eur J Cancer 46:1773–1780

    Article  CAS  Google Scholar 

  25. Scheel AH, Dietel M, Heukamp LC et al (2016) Harmonized PD-L1 immunohistochemistry for pulmonary squamous-cell and adenocarcinomas. Mod Pathol 29:1165–1172

    Article  CAS  Google Scholar 

  26. Schildhaus HU, Schultheis AM, Ruschoff J et al (2015) MET amplification status in therapy-naive adeno- and squamous cell carcinomas of the lung. Clin Cancer Res 21:907–915

    Article  CAS  Google Scholar 

  27. Shepherd FA, Domerg C, Hainaut P et al (2013) Pooled analysis of the prognostic and predictive effects of KRAS mutation status and KRAS mutation subtype in early-stage resected non-small-cell lung cancer in four trials of adjuvant chemotherapy. J Clin Oncol 31:2173–2181

    Article  CAS  Google Scholar 

  28. Sholl LM, Aisner DL, Varella-Garcia M et al (2015) Multi-institutional oncogenic driver mutation analysis in lung adenocarcinoma: the lung cancer mutation consortium experience. J Thorac Oncol 10:768–777

    Article  CAS  Google Scholar 

  29. Surati M, Patel P, Peterson A et al (2011) Role of MetMAb (OA-5D5) in c‑MET active lung malignancies. Expert Opin Biol Ther 11:1655–1662

    Article  CAS  Google Scholar 

  30. Takeuchi K, Choi YL, Togashi Y et al (2009) KIF5B-ALK, a novel fusion oncokinase identified by an immunohistochemistry-based diagnostic system for ALK-positive lung cancer. Clin Cancer Res 15:3143–3149

    Article  CAS  Google Scholar 

  31. Travis WD, Brambilla E, Noguchi M et al (2011) International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 6:244–285

    Article  Google Scholar 

  32. Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG (2015) WHO classification of tumours of the lung, pleura, thymus and heart. 4th edition. International Agency for Research on Cancer, IARC, Lyon

    Google Scholar 

  33. Vassella E, Langsch S, Dettmer MS et al (2015) Molecular profiling of lung adenosquamous carcinoma: hybrid or genuine type? Oncotarget 6:23905–23916

    Article  Google Scholar 

  34. Weissferdt A (2014) Large cell carcinoma of lung: on the verge of extinction? Semin Diagn Pathol 31:278–288

    Article  Google Scholar 

  35. Wennerberg K, Rossman KL, Der CJ (2005) The Ras superfamily at a glance. J Cell Sci 118:843–846

    Article  CAS  Google Scholar 

  36. Yoshida A, Tsuta K, Watanabe S et al (2011) Frequent ALK rearrangement and TTF-1/p63 co-expression in lung adenocarcinoma with signet-ring cell component. Lung Cancer 72:309–315

    Article  Google Scholar 

  37. Yoshizawa A, Motoi N, Riely GJ et al (2011) Impact of proposed IASLC/ATS/ERS classification of lung adenocarcinoma: prognostic subgroups and implications for further revision of staging based on analysis of 514 stage I cases. Mod Pathol 24:653–664

    Article  CAS  Google Scholar 

  38. Zhang YL, Yuan JQ, Wang KF et al (2016) The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget 7:78985–78993

    PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut für Pathologie, Uniklinik Köln, Kerpener Str. 62, 50937, Köln, Deutschland

    Maike Wittersheim, S. Schallenberg & R. Büttner

Authors
  1. Maike Wittersheim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Schallenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. Büttner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maike Wittersheim.

Ethics declarations

Interessenkonflikt

M. Wittersheim, S. Schallenberg und R. Büttner geben an, dass kein Interessenkonflikt besteht.

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wittersheim, M., Schallenberg, S. & Büttner, R. Nichtkleinzelliges Lungenkarzinom – Pathologie und Biologie. Onkologe 24, 958–966 (2018). https://doi.org/10.1007/s00761-018-0461-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00761-018-0461-5

Schlüsselwörter

Keywords

Search

Navigation