Immunohistochemical study of neoangiogenesis markers in squamous cell lung cancer

Authors

  • M. M. Baudarbekova Zaporizhzhіa State Medical University, Ukraine,

DOI:

https://doi.org/10.14739/2310-1237.2019.2.177090

Keywords:

lung neoplasms, non-small cell lung carcinoma, squamous cell carcinoma, vascular endothelial growth factor receptor-2, CD34 antigen

Abstract

 

Aim – to study VEGFR-2 and CD34 immunohistochemical expression in squamous cell lung cancer.

Materials and methods. Pathomorphological and immunohistochemical studies of surgical material from 20 patients, which were treated in ZRCOD because of SCLC, were conducted: 10 patients with SCLC without metastases in regional lymph nodes formed the I group of study and 10 patients with SCLC with metastases in regional lymph nodes formed the II group of study. 10 samples of regional lymph nodes with metastases were also examined (the III group of study). Immunohistochemical study was carried out using antibodies against VEGFR-2 and CD34.

Results. Squamous cell lung cancer is characterized by high VEGFR-2 expression marks, which are typical for I and II groups of study: 115.23 (97.35; 125.55) CUOD, 60.28 (50.77; 67.19) % and 118.33 (110.03; 140.23) CUOD, 56.56 (44.19; 67.49) %, respectively (P > 0.05). At the same time, there is statistically significant difference between the levels and the relative areas of VEGFR-2 expression in the primary tumor and in the metastases in regional lymphatic nodules (RLN) (the last one distinguished by the lower expression marks – 89.67 (67.25; 100.65) CUOD; 50.99 (41.65; 60.10) %). Tendency to increasing of the number of microvessels in the sequence “non-metastatic squamous cell lung cancer – metastatic squamous cell lung cancer – metastases in RLN” was established: 37.50 (25.00; 54.00) vs 64.50 (42.00; 102.00) vs 95.50 (76.50; 125.00), P ˂ 0.05. Presence of correlations between the following indicators was revealed: the level, the relative area of VEGFR-2 expression and the number of microvessels in non-metastatic squamous cell lung cancer (r = 0.35 and r = -0.34, respectively); the level and the relative area of VEGFR-2 expression (r = -0.45), the relative area of VEGFR-2 expression and the number of microvessels in metastatic squamous cell lung cancer (r = 0.43); the level and the relative area of VEGFR-2 expression in metastases in RLN (r = -0.44).

Conclusions. VEGFR-2 expression indices decrease from I to III groups of study, while CD34 expression increases in this sequence, moreover, the expression indices of the studied markers correlate in the primary tumor and do not correlate in regional metastases.

References

Siegel, R., Ma, J., Zou, Z., & Jemal, A. (2014) Cancer statistics, 2014. CA: A Cancer Journal for Clinicians, 64(1), 9–29. doi: 10.3322/caac.21208

Travis, W. D. (2011) Pathology of lung cancer. Clinics in Chest Medicine, 32 (2011), 669–692. doi: 10.1016/j.ccm.2011.08.005

Paduch, R. (2016) The role of lymphangiogenesis and angiogenesis in tumor metastasis. Cellular Oncology (Dordrecht), 39(5), 397–410. doi: 10.1007/s13402-016-0281-9

Holzer, T. R., Fulford, A. D., Nedderman, D. M., Umberger, T. S., Hozak, R. R., Joshi, A., et al. (2013) Tumor Cell Expression of Vascular Endothelial Growth Factor Receptor 2 Is an Adverse Prognostic Factor in Patients with Squamous Cell Carcinoma of the Lung. PLoS One, 8(11), e80292. doi: 10.1371/journal.pone.0080292

Holzer, T. R., Fulford, A. D., Reising,L. O., Nedderman, D. M., Zhang, X., Benjamin, L. E., et al. (2016) Profiling of Vascular Endothelial Growth Factor Receptor Heterogeneity Identifies Protein Expression-defined Subclasses of Human Non-small Cell Lung Carcinoma. Anticancer Research, 36(7), 3277–88.

Kather, J. N., Marx, A., Reyes-Aldasoro, C.C., Schad, L. R., Zollner, F. G., & Weis, C. (2015) Continuous representation of tumor microvessel density and detection of angiogenic hotspots in histological whole-slide images. Oncotarget, 6(22), 19163–76. doi: 10.18632/oncotarget.4383

Zhang, J., Ma, X., Li, Y., Song, Y., Ma, G., Huang, J., et al. (2016) Microvessel density as a prognostic factor in non-small cell lung cancer: a meta-analysis. International Journal of Clinical цand Experimental Medicine, 9(9), 17676–17689.

Zhao, Y. Y., Xue, C., Jiang,W., Zhao, H. Y., Huang, Y., Feenstra, K., et al. (2012) Predictive value of intratumoral microvascular density in patients with advanced non-small cell lung cancer receiving chemotherapy plus bevacizumab. Journal of Thoracic Oncology, 7(1), 71–5. doi: 10.1097/JTO.0b013e31823085f4

Ikemura, Sh., Aramaki, N., Fujii, S., Kirita, K., Umemura, Sh., Matsumoto, Sh., et al. (2017) Changes in the tumor microenvironment during lymphatic metastasis of lung squamous cell carcinoma. Cancer Science, 108(1), 136–142. doi: 10.1111/cas.13110

Tumanskyi, V. O., Yevsieiev, A. V., Kovalenko, I. S., & Zubko, M. D. (patentee) (2015) Patent 99314 Ukraina, MPK 2015.01 G01N 21/00 G06K 9/00 Sposib fototsyfrovoi morfometrii imunohistokhimichnykh preparativ [Patent of Ukraine 99314, IPC 2015.01 G01N 21/00 G06K 9/00 The technique of digital morphometry of immunohistochemical slides]. Biuleten, 10 [in Ukrainian].

Bosari, S., Lee, A. K., DeLellis, R. A., Wiley, B. D., Heatley, G. J., & Silverman, L. M. (1992) Microvessel quantitation and prognosis in invasive breast carcinoma. Human Pathology, 23, 755–761. doi: 10.1016/0046-8177(92)90344-3

Ding, M., Liu, L., Hu, Ch., Liu, Y., Qiao, Y., & Jiang, X. (2014) Expression of VEGFR2 and NRP-1 in non-small cell lung cancer and their clinical significance. Chinese Journal of Cancer Research, 26(6), 669–677. doi: 10.3978/j.issn.1000-9604.2014.12.04

Devery, A. M., Wadekar, R., Bokobza, S. M., Weber, A. M., Jiang, Y., & Ryan, A. J. (2015) Vascular endothelial growth factor directly stimulates tumour cell proliferation in non-small celllung cancer. International Journal of Oncology, 47(3), 849–56. doi: 10.3892/ijo.2015.3082

Tumanskiy, V. A., Chepets, A. V., & Kamyshnyi, А. М. (2016) Comparative characteristics of the transcriptional activity of CDH1, CTNNB1, VEGFA genes and expression of proteins E-cadherin, β-catenin and VEGFA, coded by these genes in metastatic and non-metastatic endometrioid endometrial carcinoma. Pathologia, 2, 13–18. doi: 10.14739/2310-1237.2016.2.81328

Farzam, F., Safaee, M., Oryani, M. A., Razmara, H., Fathee, N., & Farzam, V. (2017) Endothelial progenitor cells in patients with non-small cell lung cancer. Reviews in Clinical Medicine, 4(2), 50–56. doi: 10.22038/RCM.2016.6484

Aramaki, N., Ishii, G., Yamada, E., Morise, M., Aokage, K., Kojima, M., et al. (2016) Drastic morphological and molecular differences between lymph node micrometastatic tumors and macrometastatic tumors of lung adenocarcinoma. Journal of Cancer Research and Clinical Oncology, 142(1), 37–46. doi: 10.1007/s00432-015-1996-0

Sullivan, J. P., Minna, J. D., & Shay, J.W. (2010) Evidence for self-renewing lung cancer stem cells and their implications in tumor initiation, progression, and targeted therapy. Cancer Metastasis reviews, 29(1), 61–72. doi: 10.1007/s10555-010-9216-5

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Baudarbekova MM. Immunohistochemical study of neoangiogenesis markers in squamous cell lung cancer. Pathologia [Internet]. 2019Sep.2 [cited 2024Nov.2];(2). Available from: http://pat.zsmu.edu.ua/article/view/177090

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