Immunohistochemical diagnosis and prognosis of small cell lung cancer: the search for new strategies
DOI:
https://doi.org/10.15587/2519-4798.2022.253047Keywords:
small cell lung cancer, small biopsy sample, expression of p16ink4A, CD117, pathomorphosisAbstract
The aim: to find the optimal combination of immunohistochemical markers for differential diagnosis and prognosis of small cell lung cancer in small biopsy samples.
Materials and methods. The tumor specimens were divided into 3 groups: 1) 25 biopsy samples of small cell lung cancer before treatment; 2) 25 samples of small cell lung cancer procured from autopsies of patients, who underwent chemotherapy; 3) 15 biopsy samples of other lung tumors histologically similar to SCLC. All tumor samples were formalin fixed and paraffin embedded (FFPE). Immunohistochemical study performed with 5 primary antibodies: CD56, p16ink4A, TTF-1, CD117, Ki-67.
Results. TTF-1 was positive in all small cell lung cancer, lung adenocarcinomas and atypical carcinoids. Expression of CD56 was positive in 100 % of tumors from 1st group and 92 % of these tumors had more than 25 % of positive tumor cells. Expression of p16ink4A was significantly higher in 1st group than in the 3rd one (р<0,001). The stepwise logistic regression was used for finding the best markers for differential diagnosis of small cell lung cancer in small biopsy samples. The next combination of markers was chosen: TTF-1/CD56 (score 2–4)/p16 ink4A/CD117 (sensitivity – 80 %; specificity – 86.67 %; р<0,001) where “score 2–4” means expression of CD56 more than in 25 % tumor cells. Expression of Ki-67 was higher in the 2nd group compared with the 1st one (р<0,001).
Conclusion. Evaluation of p16 expression can be used as additional marker for differential diagnosis of small cell lung cancer. The following combination of markers: TTF-1/CD56 (score2-4)/p16 ink4A/CD117 could be useful in diagnosis of small cell lung cancer in small biopsy samples and in the choice of targeted chemotherapy. The further study in paired tumor samples of small cell lung cancer before and after chemotherapy is required to prove the significance of changes in expression of Ki-67, CD56, CD117 and p16ink4A
References
- Lokuhetty, D. (2021). Thoracic tumours. WHO Classification of Tumours Editorial Board. Vol. 5. Lyon: International Agency for Research on Cancer. Available at: https://publications.iarc.fr/595
- Raso, M. G., Bota-Rabassedas, N., Wistuba, I. I. (2021). Pathology and Classification of SCLC. Cancers, 13 (4), 820. doi: http://doi.org/10.3390/cancers13040820
- Schulze, A. B., Evers, G., Kerkhoff, A., Mohr, M., Schliemann, C., Berdel, W. E., Schmidt, L. H. (2019). Future Options of Molecular-Targeted Therapy in Small Cell Lung Cancer. Cancers, 11 (5), 690. doi: http://doi.org/10.3390/cancers11050690
- Nicholson, A. G., Chansky, K., Crowley, J., Beyruti, R., Kubota, K., Turrisi, A. et. al. (2016). The International Association for the Study of Lung Cancer Lung Cancer Staging Project: Proposals for the Revision of the Clinical and Pathologic Staging of Small Cell Lung Cancer in the Forthcoming Eighth Edition of the TNM Classification for Lung Cancer. Journal of Thoracic Oncology, 11 (3), 300–311. doi: http://doi.org/10.1016/j.jtho.2015.10.008
- Yang, S., Zhang, Z., Wang, Q. (2019). Emerging therapies for small cell lung cancer. Journal of Hematology & Oncology, 12 (1). doi: http://doi.org/10.1186/s13045-019-0736-3
- Bunn, P. A., Minna, J. D., Augustyn, A., Gazdar, A. F., Ouadah, Y., Krasnow, M. A. et. al. (2016). Small Cell Lung Cancer: Can Recent Advances in Biology and Molecular Biology Be Translated into Improved Outcomes? Journal of Thoracic Oncology, 11 (4), 453–474. doi: http://doi.org/10.1016/j.jtho.2016.01.012
- Koinis, F., Kotsakis, A., Georgoulias, V. (2016). Small cell lung cancer (SCLC): no treatment advances in recent years. Transl Lung Cancer Res, 5 (1), 39–50. doi: http://doi.org/10.3978/j.issn.2218-6751.2016.01.03
- Leslie, K., Wick, M. (Eds.) (2018). Practical Pulmonary Pathology: A Diagnostic Approach. Elsevier, 811. doi: http://doi.org/10.1016/c2015-0-01043-7
- Travis, W. (2015). WHO classification of tumours of the lung, pleura, thymus and heart. Lyon: Internat. Agency for Research on Cancer, 9–152.
- Švajdler, M., Mezencev, R., Ondič, O., Šašková, B., Mukenšnábl, P., Michal, M. (2018). P16 is a useful supplemental diagnostic marker of pulmonary small cell carcinoma in small biopsies and cytology specimens. Annals of Diagnostic Pathology, 33, 23–29. doi: http://doi.org/10.1016/j.anndiagpath.2017.11.008
- Dorantes-Heredia, R., Ruiz-Morales, J. M., Cano-García, F. (2016). Histopathological transformation to small-cell lung carcinoma in non-small cell lung carcinoma tumors. Translational Lung Cancer Research, 5 (4), 401–412. doi: http://doi.org/10.21037/tlcr.2016.07.10
- Shuifang, C., Zeying, Z., Jianli, Z. (2019). The effects of the combination of imatinib and crizotinib on small cell lung cancer cells expressing c-Met and c-Kit. International Journal of Clinical and Experimental Medicine, 12 (5), 4870–4878. Available at: https://e-century.us/files/ijcem/12/5/ijcem0082071.pdf
- Ramezani, M., Masnadjam, M., Azizi, A., Zavattaro, E. et. al. (2021). Evaluation of expression of c-Kit marker (CD117) in patients with squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) of the skin. AIMS Molecular Science, 8 (1), 51–59. doi: http://doi.org/10.3934/molsci.2021004
- Pelosi, G., Rindi, G., Travis, W. D., Papotti, M. (2014). Ki-67 Antigen in Lung Neuroendocrine Tumors: Unraveling a Role in Clinical Practice. Journal of Thoracic Oncology, 9 (3), 273–284. doi: http://doi.org/10.1097/jto.0000000000000092
- Inoue, K., A. Fry, E. (2018). Aberrant expression of p16INK4a in human cancers – a new biomarker? Cancer Reports and Reviews, 2 (2). doi: http://doi.org/10.15761/crr.1000145
- Pelosi, G., Masullo, M., Leon, M. E., Veronesi, G., Spaggiari, L., Pasini, F. et. al. (2004). CD117 immunoreactivity in high-grade neuroendocrine tumors of the lung: a comparative study of 39 large-cell neuroendocrine carcinomas and 27 surgically resected small-cell carcinomas. Virchows Archiv, 445 (5), 449–455. doi: http://doi.org/10.1007/s00428-004-1106-1
- Jha, V., Sharma, P., Mandal, A. (2017). Utility of Cluster of Differentiation 5 and Cluster of Differentiation 117 Immunoprofile in Distinguishing Thymic Carcinoma from Pulmonary Squamous Cell Carcinoma: A Study on 1800 Nonsmall Cell Lung Cancer Cases. Indian Journal of Medical and Paediatric Oncology, 38 (4), 430–433. doi: http://doi.org/10.4103/ijmpo.ijmpo_148_16
- Huang, Y., Chang, Y., Wu, C. (2019). EP1.09-10 A Diagnostic Pitfall in Posterior Mediastinal Tumor: Expression of CD117 in Atypical Ewing Sarcoma Masquerading as Classic Seminoma. Journal of Thoracic Oncology, 14 (10), S1001–S1002. doi: http://doi.org/10.1016/j.jtho.2019.08.2206
- Ishibashi, N., Maebayashi, T., Aizawa, T., Sakaguchi, M., Nishimaki, H., Masuda, S. (2017). Correlation between the Ki-67 proliferation index and response to radiation therapy in small cell lung cancer. Radiation Oncology, 12 (1). doi: http://doi.org/10.1186/s13014-016-0744-1
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2022 Irina Yakovtsova, Olexandr Yanchevskyi, Taisiia Chertenko, Andriy Kis, Andrii Oliyinyk

This work is licensed under a Creative Commons Attribution 4.0 International License.
Our journal abides by the Creative Commons CC BY copyright rights and permissions for open access journals.
Authors, who are published in this journal, agree to the following conditions:
1. The authors reserve the right to authorship of the work and pass the first publication right of this work to the journal under the terms of a Creative Commons CC BY, which allows others to freely distribute the published research with the obligatory reference to the authors of the original work and the first publication of the work in this journal.
2. The authors have the right to conclude separate supplement agreements that relate to non-exclusive work distribution in the form in which it has been published by the journal (for example, to upload the work to the online storage of the journal or publish it as part of a monograph), provided that the reference to the first publication of the work in this journal is included.