×
Home Current Archive Editorial board
News Contact
Review paper

Prevalence of epidermal growth factor receptor (EGFR) mutations and correlation with histological patterns in lung adenocarcinoma in patients from Bosnia and Herzegovina

By
Dalma Udovičić-Gagula Orcid logo ,
Dalma Udovičić-Gagula
Contact Dalma Udovičić-Gagula

Department of Pathology and Cytology, Clinical Centre University in Sarajevo, Sarajevo, Bosnia and Herzegovina

Nejra Džananović ,
Nejra Džananović

Department of Clinic Biochemistry and Immunology, Clinical Centre University of Sarajevo, Sarajevo, Bosnia and Herzegovina

Mirsad Dorić
Mirsad Dorić

Department of Pathology, School of Medicine, University of Sarajevo, Sarajevo, Bosnia and Herzegovina

Abstract

Aim
Lung adenocarcinoma (ADC) is a leading subtype of lung cancer, histologically defined with five different architectural
growth patterns: lepidic, acinar, papillary, solid and micropapillary. The aim of this study was to explore the prevalence of epidermal growth factor receptor (EGFR) mutation and a relationship between the specific histological patterns of lung ADC in the population of Bosnia and Herzegovina.
Methods
The study included tumour tissue from 102 patients with completely resected lung ADC from 2015 to 2020. Molecular testing for the presence of EGFR mutations was performed by real-time PCR method. The relationship between EGFR mutation status and clinicopathological parameters was analysed.
Results
The EGFR mutation was detected in 12 (11.8%) cases of ADC, more often in non-smokers (p=0.007). A higher percentage
of solid growth pattern presented in ADC may be an indicator of EGFR negativity (p=0.039), while a higher percentage of micropapillary growth pattern more common in the presence of EGFR mutation (p=0.047).
Conclusion
The prevalence of EGFR mutation is in accordance with the expected prevalence considering our studied population,
Caucasians from South Europe. Better understanding of the relationship between histological patterns and molecular characteristics of lung ADC will enable earlier diagnosis and optimal treatment for patients.

References

1.
Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M. Global Cancer Observatory: Cancer Today. 2020.
2.
World Cancer Research Fund International. Lung cancer statistics. 2023.
3.
Travis WD, E B, AP B, AP B, A M, AG N. WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart. 2015.
4.
Lindeman NI, Cagle PT, Beasley MB, Chitale DA, Dacic S, Giaccone G, et al. Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. Vol. 8, J Thorac Oncol. 2013. p. 823–59.
5.
Chevallier M, Borgeaud M, Addeo A, Friedlaender A. Oncogenic driver mutations in non-small cell lung cancer: past, present and future. Vol. 12, World J Clin Oncol. 2021. p. 217–37.
6.
Bell DW, Branningan BW, Matsuo K, Finkelstein DM, Sordella R, Settleman J, et al. Increased prevalence of EGFR-mutant lung cancer in women and in East Asian populations: analysis of estrogen-related polymorphisms. Vol. 14, Clin Cancer Res. 2008. p. 4079–84.
7.
Graham RP, Treece AL, Lindeman NI, Vasalos P, Shan M, Jennings LJ, et al. Worldwide frequency of commonly detected EGFR mutations. Vol. 142, Arch Pathol Lab Med. 2018. p. 163–7.
8.
Zou J, Bella AE, Chen Z, Han X, Su C, Lei Y, et al. Frequency of EGFR mutations in lung adenocarcinoma with malignant pleural effusion: Implication of cancer biological behaviour regulated by EGFR mutation. Vol. 42, J Int Med Res. 2014. p. 1110–7.
9.
Song Z, Zhu H, Guo Z, Wu W, W S, Zhang Y. Correlation of EGFR mutation and predominant histologic subtype according to the new lung adenocarcinoma classification in Chinese patients. Vol. 30, Med Oncol. 2013.
10.
Yoshizawa A, Sumiyoshi S, Sonobe M, Kobayashi M, Fujimoto M, Kawakami F, et al. Validation of the IASLC/ATS/ERS lung adenocarcinoma classification for prognosis and association with EGFR and KRAS gene mutations: analysis of 440 Japanese patients. Vol. 8, J Thorac Oncol. 2013. p. 52–61.
11.
Russell PA, Barnett SA, Walkiewicz M, Wainer Z, Conron M, Wright GM, et al. Correlation of mutation status and survival with predominant histologic subtype according to the new IASLC/ ATS/ERS lung adenocarcinoma classification in stage III (N2) patients. Vol. 8, J Thorac Oncol. 2013. p. 461–8.
12.
Cai YR, Dong YJ, Wu HB, Liu ZC, Zhou LJ, Su D, et al. Micropapillary: A component more likely to harbour heterogeneous EGFR mutations in lung adenocarcinomas. Vol. 6, Sci Rep. 2016.
13.
Zhang H, Huang W, Liu C, Giaccone G, Zhao X, Sun X, et al. The prognostic value of non-predominant micropapillary pattern in a large cohort of resected invasive lung adenocarcinoma measuring ≤3 cm. Vol. 11, Front Oncol. 2021.
14.
Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, et al. In: AJCC Cancer Staging Manual. 2017.
15.
Fischer AH, Jacobson KA, Rose J, Zeller R. Hematoxylin and eosin staining of tissue and cell sections. CSH Protoc. 2008.
16.
Udovicic-Gagula D. Analysis of frequency of EGFR and ALK mutations, and PD-L1 expression in patients with lung adenocarcinoma in Bosnia and Herzegovina. In: Abstracts of 32nd Congress of the European society of pathology and XXXIII International congress of the International academy of pathology. 2020. p. 126–7.
17.
Berois N, Touya D, Ubillos L, Bertoni B, Osinaga E, Varangot M. Prevalence of EGFR mutations in lung cancer in Uruguayan population. Vol. 2017, J Cancer Epidemiol. 2017.
18.
Graham RP, Treece AL, Lindeman NI, Vasalos P, Shan M, Jennings LJ, et al. Worldwide frequency of commonly detected EGFR mutations. Vol. 142, Arch Pathol Lab Med. 2018. p. 163–7.
19.
Takeda K, Yamasaki A, Igishi T, Kawasaki Y, ItoNishii S, Izumi H, et al. Frequency of epidermal growth factor receptor mutation in smokers with lung cancer without pulmonary emphysema. Vol. 37, Anticancer Res. 2017. p. 765–71.
20.
Prabhakar CN. Epidermal growth factor receptor in non-small cell lung cancer. Vol. 4, Transl Lung Cancer Res. 2015. p. 110–8.
21.
Lee CK, Brown C, Gralla RJ, Hirsh V, Thongprasert S, Tsai CM, et al. Impact of EGFR inhibitor in non-small cell lung cancer on progression-free and overall survival: a meta-analysis. Vol. 105, J Natl Cancer Inst. 2013. p. 595–605.
22.
Kobayashi Y, Mitsudomi T. Not all epidermal growth factor receptor mutations in lung cancer are created equal: Perspectives for individualized treatment strategy. Vol. 107, Cancer Sci. 2016. p. 1179–86.
23.
Zhang T, Wan B, Zhao Y, Li C, Liu H, Lv T, et al. Treatment of uncommon EGFR mutations in non-small cell lung cancer: new evidence and treatment. Vol. 8, Transl Lung Cancer Res. 2019. p. 302–16.
24.
Park K, Tan EH, O’Byrne K, Zhang L, Boyer M, Mok T, et al. Afatinib versus gefitinib as first-line treatment of patients with EGFR mutationpositive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial. Vol. 17, Lancet Oncol. 2016. p. 577–89.
25.
Wu YL, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, et al. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Vol. 18, Lancet Oncol. 2017. p. 1454–66.
26.
Kobayashi Y, Togashi Y, Yatabe Y, Mizuuchi H, Jangchul P, Kondo C, et al. EGFR exon 18 mutations in lung cancer: molecular predictors of augmented sensitivity to afatinib or neratinib as compared with first- or third-generation TKIs. Vol. 21, Clin Cancer Res. 2015. p. 5305–13.
27.
Robichaux JP, Elamin YY, Tan Z, Carter BW, Zhang S, Liu S, et al. Mechanisms and clinical activity of an EGFR and HER2 exon 20-selective kinase inhibitor in non-small cell lung cancer. Vol. 24, Nat Med. 2018. p. 638–46.
28.
Yasuda H, Park E, Yun CH, Sng NJ, Lucena-Araujo AR, Yeo WL, et al. Structural, biochemical, and clinical characterization of epidermal growth factor receptor.
29.
Naidoo J, Sima CS, Rodriguez K, Busby N, Nafa K, Ladanyi M, et al. Epidermal growth factor receptor exon 20 insertions in advanced lung adenocarcinomas: Clinical outcomes and response to erlotinib. Vol. 121, Cancer. 2015. p. 3212–20.
30.
Spira A, Ramalingam SS, Neal J. Mobocertinib in EGFR exon 20 insertion-positive metastatic NSCLC patients with disease control on prior EGFR TKI therapy. Vol. A15, In proceedings of 2021 World Conference on Lung Cancer.
31.
Ramalingam SS, Zhou C, Kim TM, Kim S, Yang JC, Riely GJ, et al. Mobocertinib (TAK-788) in EGFR exon 20 insertion (ex20ins)+ metastatic NSCLC (mNSCLC): additional results from platinumpretreated patients (pts) and EXCLAIM cohort of phase 1/2 study. Vol. 39, J Clin Oncol. 2021.
32.
FDA grants accelerated approval to mobocertinib for metastatic non-small cell lung cancer with EGFR exon 20 insertion mutations. 2023.
33.
Olivier T, Prasad V. Amivantamab and mobocertinib in exon 20 insertions EGFR mutant lung cancer, challenge to the current guidelines. Vol. 23, Transl Oncol. 2022.
34.
Evans M, O’Sullivan B, Smith M, Hughes F, Mullis T, Trim N, et al. Large-scale EGFR mutation testing in clinical practice: analysis of a series of 18,920 non-small cell lung cancer cases. Vol. 25, Pathol Oncol Res. 2019. p. 1401–9.
35.
Zhang T, Wan B, Zhao Y, Li C, Liu H, Lv T, et al. Treatment of uncommon EGFR mutations in non-small cell lung cancer: new evidence and treatment. Vol. 8, Transl Lung Cancer Res. 2019. p. 302–16.
36.
Goss G, Tsai CM, Shepherd FA, Bazhenova L, Lee JS, Chang GC, et al. Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer (AURA2): a multicentre, open-label, single-arm, phase 2 study. Vol. 17, Lancet Oncol. 2016. p. 1643–52.
37.
Prabhakar CN. Epidermal growth factor receptor in non-small cell lung cancer. Vol. 4, Transl Lung Cancer Res. 2015. p. 110–8.
38.
Arrieta O, Cardona AF, Martín C, Más-López L, Corrales-Rodríguez L, Bramuglia G, et al. Updated frequency of EGFR and KRAS mutations in non-small-cell lung cancer in Latin America: The Latin-American Consortium for the Investigation of Lung Cancer (CLICaP. Vol. 10, J Thorac Oncol. 2015. p. 838–43.
39.
Boukansa S, Benbrahim Z, Gamrani S, Bardai S, Bouguenouch L, Mazti A, et al. Correlation of epidermal growth factor receptor mutation with major histologic subtype of lung adenocarcinoma according to IASLC/ATS/ERS classification.
40.
Dong YJ, Cai YR, Zhou LJ, Su D, Mu J, Chen XJ, et al. Association between the histological subtype of lung adenocarcinoma, EGFR/KRAS mutation status and the ALK rearrangement according to the novel IASLC/ATS/ERS classification. Vol. 11, Oncol Lett. 2016. p. 2552–8.
41.
Levy M, Lyon L, Barbero E, Wong J, Suga JM, Sam D, et al. Histologic grade is predictive of incidence of epidermal growth factor receptor mutations in metastatic lung adenocarcinoma.
42.
Chao L, Yi-Sheng H, Yu C, Li-Xu Y, Xin-Lan L, Dong-Lan L, et al. Relevance of EGFR mutation with micropapillary pattern according to the novel IASLC/ATS/ERS lung adenocarcinoma classification and correlation with prognosis in Chinese patients. Vol. 86, Lung Cancer. 2014. p. 164–9.
43.
Matsumura M, Okudela K, Kojima Y, Umeda S, Tateishi Y, Sekine A, et al. A Histopathological feature of EGFR-mutated lung adenocarcinomas with highly malignant potential - an implication of micropapillary element. Vol. 11:e0166795, PLoS One. 2016.
44.
Molina Y, P C, SD S, SE A, A.A. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Vol. 83, Mayo Clin Proc. 2008. p. 584–94.

Citation

Authors retain copyright. This work is licensed under a Creative Commons Attribution 4.0 International License. Creative Commons License

 

Article metrics

Google scholar: See link

The statements, opinions and data contained in the journal are solely those of the individual authors and contributors and not of the publisher and the editor(s). We stay neutral with regard to jurisdictional claims in published maps and institutional affiliations.