Histological trends and molecular genetic features of non-small cell lung cancer in the Khanty-Mansiysk autonomous district – Ugra

Objective: to study the histological structure of lung cancer, as well as molecular-genetic, gender, demographic and anamnestic characteristics of patients with non-small cell lung cancer in Khanty-Mansiysk Autonomous district – Ugra. Material and Methods. Material for the study consisted of 6725 cases of lung cancer for the period 2001–2020 and 266 cases diagnosed with non-small cell lung cancer for the period 2020–2023. Nonparametric Fisher’s criterion and χ2 test were used to analyze statistical factors. The relative risk of an event in the main group compared to the control group was calculated. Results. Squamous cell carcinoma remained the most common histological form among lung cancers detected for the periods 2001–2010 and 2011–2020 (40.2 and 38.3 %, respectively). During the second decade of the study period, the proportion of lung adenocarcinoma increased by 9.6%, approaching the rates of squamous cell lung carcinoma. It should be noted that in the structure of all histologic subtypes of non-small cell lung cancer, genetic aberrations occurred more frequently in adenocarcinoma than in other histologic forms of lung cancer (33 vs 6 %, respectively). The results of the analysis showed that the relative risk of developing genetic aberrations in EGFR, KRAS, ALK oncogenes was respectively 21.08; 9.04 and 10.84 times higher in lung adenocarcinoma and 15.87; 2.18 and 10.2 times higher among never smokers than in the control groups. The incidence of mutations in the EGFR gene was statistically more frequent in women (p<0.001), and the incidence of translocation in the AL K gene was predominantly diagnosed at age ≥48 years (p=0.002) regardless of gender. The specificity of PD-L1 expression levels (low – 63.2 %, medium – 16.2 %, high – 4.5 %) is consistent with other recent studies. Conclusion. The study of molecular-genetic changes observed in patients with non-small-cell lung cancer in Ugra allows the development of organizational and methodological approaches to diagnosis and treatment of these patients.

1. Cancer care for the population of Russia in 2020. Ed. by A.D. Kaprin, V.V. Starinsky, A.O. Shakhzadova. Moscow, 2021. 239 p. (in Russian).

2. Goldstraw P., Chansky K., Crowley J., Rami-Porta R., Asamura H., Eberhardt W.E., Nicholson A.G., Groome P., Mitchell A., Bolejack V.; International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee, Advisory Boards, and Participating Institutions; International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee Advisory Boards and Participating Institutions. The IASLC Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Lung Cancer. J Thorac Oncol. 2016; 11(1): 39–51. doi: 10.1016/j.jtho.2015.09.009.

3. GLOBOCAN 2020: estimated cancer incidence, mortality and prevalence worldwide in 2020 [Internet]. International Agency for Research on Cancer, World Health Organization, 2018. [cited 2024 Apr 1]. URL: http://globocan.iarc.fr/.

4. Mordovskii A.A., Aksarin A.A., Parsadanyan A.M., Ter-Ovanesov M.D., Troyan P.P. Epidemiologic characteristics of morbidity and mortality from lung cancer in Khanty-Mansi Autonomous Okrug – Yugra. Siberian Journal of Oncology. 2021; 20(4): 30–8. (in Russian). doi: 10.21294/1814-4861-2021-20-4-30-38.

5. Heighway J., Betticher D.C. Solid Tumour Section Mini Review Atlas of Genetics and Cytogenetics in Oncology and Haematology Lung tumors: an overview. Atlas Genet Cytogenet Oncol Haematol. 2004; 8(2).

6. Smirnova E.A, Pavlovskaya A.I., Raikhlin N.T., Polotskii B.E., Sviridov S.V., Laktionov K.K., Gerasimov S.S. Morphologic criteria of large cell lung cancer: diagnosis and prognosis. Herald RONC named after N.N. Blokhin of the Russian Academy of Medical Sciences. 2008; 19(3): 57–63. (in Russian).

7. Zheng M. Classification and Pathology of Lung Cancer. Surg Oncol Clin N Am. 2016; 25(3): 447–68. doi: 10.1016/j.soc.2016.02.003.

8. Aksarin A.A., Ter-Ovanesov M.D., Mordovskiy A.A. Aspects of surgical treatment of non-small cell lung cancer. Surgeon. 2014; 7: 20–7. (in Russian).

9. Aksyonova I.A., Domozhirova A.S., Novikova T.S. Analysis of survival of patients with lung cancer in the Chelyabinsk region. Effective Pharmacotherapy. 2019; 15(3): 18–22. (in Russian).

10. Imyanitov E.N., Khanson K.P. Molecular Oncology: Clinical Aspects. St. Petersburg, 2007. 213 p. (in Russian).

11. Merabishvili V.M., Barchuk A.S., Barchuk A.A., Atroshchenko A.V., Shcherbakov A.M., Tarkov S.A., Arsen’ev A.I., Demin E.V., Merabishvili E.N., Preis V.G., Kharitonov M.V., Chepik O.F. Morbidity, diagnosis, dynamics of the histological structure, the effectiveness of lung cancer treatment of patients in different age and gender groups at the present stage. Preventive and Clinical Medicine. 2015; 3(56): 88–97. (in Russian).

12. Ettinger D.S., Wood D.E., Aisner D.L., Akerley W., Bauman J., Chirieac L.R., D’Amico T.A., DeCamp M.M., Dilling T.J., Dobelbower M., Doebele R.C., Govindan R., Gubens M.A., Hennon M., Horn L., Komaki R., Lackner R.P., Lanuti M., Leal T.A., Leisch L.J., Lilenbaum R., Lin J., Loo B.W. Jr, Martins R., Otterson G.A., Reckamp K., Riely G.J., Schild S.E., Shapiro T.A., Stevenson J., Swanson S.J., Tauer K., Yang S.C., Gregory K., Hughes M. Non-Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2017; 15(4): 504–35. doi: 10.6004/jnccn.2017.0050.

13. Friedlaender A., Banna G., Patel S., Addeo A. Diagnosis and Treatment of ALK Aberrations in Metastatic NSCLC. Curr Treat Options Oncol. 2019; 20(10): 79. doi: 10.1007/s11864-019-0675-9.

14. Mok T.S., Wu Y.L., Thongprasert S., Yang C.H., Chu D.T., Saijo N., Sunpaweravong P., Han B., Margono B., Ichinose Y., Nishiwaki Y., Ohe Y., Yang J.J., Chewaskulyong B., Jiang H., Duffield E.L., Watkins C.L., Armour A.A., Fukuoka M. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009; 361(10): 947–57. doi: 10.1056/NEJMoa0810699.

15. Planchard D., Besse B., Groen H.J.M., Hashemi S.M.S., Mazieres J., Kim T.M., Quoix E., Souquet P.J., Barlesi F., Baik C., Villaruz L.C., Kelly R.J., Zhang S., Tan M., Gasal E., Santarpia L., Johnson B.E. Phase 2 Study of Dabrafenib Plus Trametinib in Patients With BRAF V600E-Mutant Metastatic NSCLC: Updated 5-Year Survival Rates and Genomic Analysis. J Thorac Oncol. 2022; 17(1): 103–15. doi: 10.1016/j.jtho.2021.08.011.

16. Wakelee H.A., Altorki N.K., Zhou C., Csőszi T., Vynnychenko I.O., Goloborodko O., Luft A., Akopov A., Martinez-Marti A., Kenmotsu H., Chen Y.M., Chella A., Sugawara S., Gitlitz B.J., Bennett E., Wu F., Yi J., Deng Y., McCleland M., Felip E. IMpower010: Primary results of a phase III global study of atezolizumab versus best supportive care after adjuvant chemotherapy in resected stage IB–IIIA non-small cell lung cancer (NSCLC). J Clin Oncol. 2021; 39(15sl). doi: 10.1200/JCO.2021.39.15_suppl.8500.

17. Wu Y.L., Tsuboi M., He J., John T., Grohe C., Majem M., Goldman J.W., Laktionov K., Kim S.W., Kato T., Vu H.V., Lu S., Lee K.Y., Akewanlop C., Yu C.J., de Marinis F., Bonanno L., Domine M., Shepherd F.A., Zeng L., Hodge R., Atasoy A., Rukazenkov Y., Herbst R.S.; ADAURA Investigators. Osimertinib in Resected EGFR-Mutated Non-Small-Cell Lung Cancer. N Engl J Med. 2020; 383(18): 1711–23. doi: 10.1056/NEJMoa2027071.

18. Zappa C., Mousa S.A. Non-small cell lung cancer: current treatment and future advances. Transl Lung Cancer Res. 2016; 5(3): 288–300. doi: 10.21037/tlcr.2016.06.07.

19. Shneider O.V., Kamilova T.A., Golota A.S., Sarana A.M., Shcherbak S.G. Biomarkers and targeting therapy in lung cancer. Physical and Rehabilitation Medicine, Medical Rehabilitation. 2021; 3(1): 74–94. (in Russian).

20. Han B., Tjulandin S., Hagiwara K., Normanno N., Wulandari L., Laktionov K., Hudoyo A., He Y., Zhang Y.P., Wang M.Z., Liu C.Y., Ratcliffe M., McCormack R., Reck M. EGFR mutation prevalence in AsiaPacific and Russian patients with advanced NSCLC of adenocarcinoma and non-adenocarcinoma histology: The IGNITE study. Lung Cancer. 2017; 113: 37–44. doi: 10.1016/j.lungcan.2017.08.021.

21. Harrison P.T., Vyse S., Huang P.H. Rare epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer. Semin Cancer Biol. 2020; 61: 167–79. doi: 10.1016/j.semcancer.2019.09.015.

22. Imyanitov E.N., Demidova I.A., Gordiev M.G., Filipenko M.L., Kekeyeva T.V., Moliaka Y.K., Gervas P.A., Kozhemyako V.B., Vodolazhskiy D.I., Sergeyeva L.A., Fattakhova D.U., Iyevleva A.G., Mitiushkina N.V., Kuligina E.Sh., Barinov A.A., Mommaeva M.S., Aleksakhina S.N., Tsimafeyeu I.V., Tjulandin S.A. Distribution of EGFR Mutations in 10,607 Russian Patients with Lung Cancer. Mol Diagn Ther. 2016; 20(4): 401–6. doi: 10.1007/s40291-016-0213-4.

23. Pawelczyk K., Piotrowska A., Ciesielska U., Jablonska K., GletzelPlucinska N., Grzegrzolka J., Podhorska-Okolow M., Dziegiel P., Nowinska K. Role of PD-L1 Expression in Non-Small Cell Lung Cancer and Their Prognostic Significance according to Clinicopathological Factors and Diagnostic Markers. Int J Mol Sci. 2019; 20(4): 824. doi: 10.3390/ijms20040824.