Yakovtsova I., Yanchevskiy O., Chertenko T., Dolgaia O., Oliynyk A.


About the author:

Yakovtsova I., Yanchevskiy O., Chertenko T., Dolgaia O., Oliynyk A.



Type of article:

Scentific article


Lung cancer is the most common cause of cancer-related deaths worldwide in adults. It is divided into two big histological groups: small cell lung cancer (SCLC) and non-SCLC (NSCLC). The updated 2015 WHO classification of lung tumors focuses on molecular profiles of different types of lung cancers and usage of this data not only for differential diagnosis, but also for molecular-targeted therapy. Nowadays, the main goal for pathologists is the good understanding of molecular and genetic features of all histological types of lung cancers. Moreover, they should navigate freely through the wide spectrum of diagnostic methods, those give a possibility to find these molecular and genetic features. The aim of our study to analyze the modern concepts about molecular features of lung cancers and their influence on the moleculobiological testing of this group of tumors. Object and methods. The information was collected from different scientific databases such as: Scopus, Web of Science, PubMed, Google Scholar, MEDLINE, Medscape. Bibliosemantic method and content analysis were used for information searching. The points of our interest were data about molecular features of different types of lung tumors and novel data about methods of molecular and biological diagnostics of these tumors, such as molecular testing, immunohistochemical analysis and liquid biopsy. Results. In our study we described 18 significant mutations for lung adenocarcinomas, 11 significant mutations for squamous cell carcinomas and some molecular pathways that are able to play an important role in tumor growth of SCLC and development of chemoresistance. In this article we also describe all methods of liquid biopsy that can be used in diagnostic and prognostic schemes for lung cancers. These methods include not only finding the circulating tumor cells, but also detection such tumor components as circulating tumor DNA, microRNA in exosomes and usage of platelets as the source of tumor-RNA. Conclusion. The modern pathomorphological examination of lung cancers are not able without evaluation of their molecular features, because it is an important part not only for the accurate histological diagnosis, but also for the choice of correct treatment. The modern pathomorphological methods include molecular testing, immunohistochemical analysis and liquid biopsy. The most prominent breakthrough was made in the field of NSCLC. Due to novel molecular data testing for EGFR mutation and ALK rearrangement is recommended in lung tumors classified as adenocarcinoma and in cases where an adenocarcinoma component cannot be excluded. The key molecular targets for SCLC, the influence on that would allow to treat this type of tumor effectively, still are not found.


non-small cell lung carcinoma, small cell lung carcinoma, molecular features, immunohistochemical testing, liquid biopsy


  1.  Lozano R, Naghavi M, Foreman K. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380:2095-128.
  2. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87-108. DOI: 10.3322/ caac.21262
  3. Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG. WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart. 4th ed. Lyon: IARC (2015).
  4.  Travis W, Brambilla E, Nicholson A, Yatabe Y, Austin J, Beasley M, et al. The 2015 World Health Organization Classification of Lung Tumors. Journal of Thoracic Oncology. 2015;10(9):1243-60.
  5. The Cancer Genome Atlas Research Network. Comprehensive genomic char-acterization of squamous cell lung cancers. Nature. 2012;489(7417):519-25. DOI: 10.1038/nature11404
  6. The Cancer Genome Atlas Research Network. Comprehensive molecular pro-filing of lung adenocarcinoma. Nature. 2014;511(7511):543-50. DOI: 10.1038/ nature13385
  7. Inamura K. Lung Cancer: Understanding Its Molecular Pathology and the 2015 WHO Classification. Frontiers in Oncology. 2017;7.
  8. Leonetti A, Facchinetti F, Minari R, Cortellini A, Rolfo C, Giovannetti E, et al. Notch pathway in small-cell lung cancer: from preclinical evidence to therapeutic challenges. Cellular Oncology. 2019;42(3):261-73.
  9. Rolfo C, Castiglia M, Perez A, Reclusa P, Pauwels P, Sober L, et al. Liquid Biopsy in Non-Small Cell Lung Cancer (NSCLC). Current Clinical Pathology. 2017:103-15.
  10. Maheswaran S, Sequist LV, Nagrath S, Ulkus L, Brannigan B, Collura CV, et al. Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med [Internet]. Massachusetts Medical Society. 2008;359(4):366-77. Available from: http://dx.doi.org/10.1056/NEJMoa0800668
  11. Punnoose EA, Atwal S, Liu W, Raja R, Fine BM, Hughes BGM, et al. Evaluation of circulating tumor cells and circulating tumor DNA in non-small cell lung cancer: association with clinical endpoints in a phase II clinical trial of pertuzumab and erlotinib. Clin Cancer Res. United States. 2012;18(8):2391-401.
  12.  Chen K-Z, Lou F, Yang F, Zhang J-B, Ye H, Chen W, et al. Circulating tumor DNA detection in early-stage non-small cell lung cancer patients by targeted sequencing. Sci Rep. England. 2016;6:31985.
  13. Dietz S, Schirmer U, Merce C, von Bubnoff N, Dahl E, Meister M, et al. Low input whole-exome sequencing to determine the representation of the tumor exome in circulating DNA of non-small cell lung cancer patients. PLoS One. United States. 2016;11(8):e0161012.
  14. Wang W, Song Z, Zhang Y. A comparison of ddPCR and ARMS for detecting EGFR T790M status in ctDNA from advanced NSCLC patients with acquired EGFR-TKI resistance. Cancer Med. 2017 Jan;6(1):154-62.
  15. Giallombardo M, Chacбrtegui Borrбs J, Castiglia M, Van Der Steen N, Mertens I, Pauwels P, et al. Exosomal miRNA analysis in non-small cell lung cancer (NSCLC) patients’ plasma through qPCR: a feasible liquid biopsy tool. JVisExp. 2016;111:e53900. Available from: http://www.jove. com/video/53900
  16. Reclusa P, Sirera R, Araujo A, Giallombardo M, Valentino A, Sorber L, et al. Exosomes genetic cargo in lung cancer: a truly Pandora’s box. Transl lung cancer Res. China. 2016;5(5):483-9.
  17. 17.Sandfeld-Paulsen B, Aggerholm-Pedersen N, Bжk R, Jakobsen KR, Meldgaard P, Folkersen BH, et al. Exosomal proteins as prognostic biomarkers in non-small cell lung cancer. Mol Oncol [Internet]. 201610(10):1595-602. Available from: http://www.sciencedirect.com/science/article/pii/ S1574789116301235
  18. Nilsson RJA, Karachaliou N, Berenguer J, Gimenez-Capitan A, Schellen P, Teixido C, et al. Rearranged EML4-ALK fusion transcripts sequester in circulating blood platelets and enable blood-based crizotinib response monitoring in non-small-cell lung cancer. Oncotarget. United States. 2016;7(1):1066-75.
  19. Tamminga M, Groen H, Hiltermann T. Circulating tumor cells as a liquid biopsy in small cell lung cancer, a future editorial. Translational Cancer Research. 2017;6(S2):353-6.
  20. Lok BH, Gardner EE, Schneeberger VE. PARP inhibitor activity correlates with SLFN11 expression and demonstrates synergy with temozolomide in small cell lung cancer. Clin Cancer Res. 2017;23:523-35.
  21. Allison Stewart C, Tong P, Cardnell RJ, Sen T, Li L, Gay CM, et al. Dynamic variations in epithelial-to mesenchymal transition (EMT), ATM, and SLFN11 govern response to PARP inhibitors and cisplatin in small cell lung cancer. Oncotarget. 2017;8:28575-87.
  22. Carolyn Glass, Philippe Joubert, Paul JL Zhang. Lung tumor [Internet]. PathologyOutlines.com. 2019 [cited 17 June 2019]. Available from: https://www.pathologyoutlines.com/lungtumor.html
  23.  Inamura K, Satoh Y, Okumura S, Nakagawa K, Tsuchiya E, Fukayama M, et al. Pulmonary adenocarcinomas with enteric differentiation: histologic and immunohistochemical characteristics compared with metastatic colorectal cancers and usual pulmonary adenocarcinomas. Am J Surg Pathol. 2005;29(5):660-5. DOI: 10.1097/01.pas.0000160438.00652.8b
  24. Sabari JK, Lok BH, Laird JH, Poirier JT, Rudin CM. Unravelling the biology of SCLC: implications for therapy. Nat Rev Clin Oncol. 2017;14:549-61.

Publication of the article:

«Bulletin of problems biology and medicine» Issue 3 (152), 2019 year, 41-45 pages, index UDK 616.24-006.6-091.8+577.21