Prognostic aspects of immunohistochemical assessment of cellular renewal and transcription factor SOX2 with precancerous changes in the gastric mucosa depending on the genotype of Helicobacter pylori in patients with various types of chronic gastritis


  • D. Sukhan
  • S. Vernigorodskiy
Keywords: Helicobacter pylori, chronic gastritis, morphological changes, immunohistochemical analysis, Ki-67, Cyclin D1, p53, CPP32, HER2, transcription factor Sox2.

Abstract

The precancerous potential of chronic gastritis (CG) associated with H. pylori is discussed in numerous writings, and today, CG is central to precancerous conditions of the stomach. A convincing theoretical basis for such an assessment of chronic gastritis is its characteristic feature — an interruption of cell renewal with the proliferation phase predominating over the differentiation phase. However, the determination of the degree of proliferative activity and impaired differentiation of the epithelium of the gastric mucosa (GM) remains not fully understood. The goal of our study was the immunohistochemical evaluation of the expression of Ki-67, Cyclin D1, p53, CPP32, HER2 and the Sox2 transcription factor in GM epithelial cells in patients with H. pylori-associated chronic gastritis.. To accomplish this goal, histological, cytological, immunohistochemical, molecular genetic, morphometric and statistical research methods were used. We found that in chronic H. pylori-associated non-atrophic gastritis (CNG) compared with H. pylori (-), the GM epithelium renewal rate increased, characterized by a significant increase in the expression of caspase-3 and Ki-67 proliferation markers, cyclin D1 (p <0.001) with expansion of the proliferative compartment and apoptosis zones. Ki-67, Cyclin D1, and p53 expression in severe dysplasia (SD) of GM was significantly (p <0.05) higher than the mild in patients with chronic non-atrophic and atrophic H. pylori-associated gastritis, despite a decrease in the expression of the transcription factor Sox2 and caspase-3 in cases of SD. The most specific marker for determining SD in patients with H. pylori-associated chronic gastritis was marker p53 (sensitivity 98.73%; specificity 83.38%, confidence interval 95%, p <0.05). Considering the immunohistochemical markers of H. pylori, a screening system has been developed for the early diagnosis of precancerous changes in the GM that will help optimize the treatment tactics of patients with chronic gastritis and increase the efficiency of detecting dysplastic and atrophic changes in the GM at their early stages of development.

References

1. Abrahao-Machado, L. F. & Scapulatempo-Neto, C. (2016). HER2 testing in gastric cancer: An update. World J. Gastroenterol., 22 (19), 4619–25. doi: 10.3748/wjg.v22.i19.4619.

2. Agoston, A. T. & Odze, R. D. (2014) Evidence that gastric pit dysplasia-like atypia is a neoplastic precursor lesion. Hum. Pathol., 45 (3), 446–55. doi: 10.1016/j.humpath.2013.10.032.

3. Ashktorab, H., Dashwood, R., Dashwood, M. M. & Zaidi, S. I. (2009). H. pylori -Induced Apoptosis in Human Gastric Cancer Cells Mediated via the Release of Apoptosis-Inducing Factor from Mitochondria. Helicobacter, 13 (6), 506–17. doi: 10.1111/j.1523-5378.2008.00646.

4. Bosman, F. T., Carneiro, F., Hruban, R. H. & Theise, N. D. (2010). World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Digestive System. IARC Press. Lyon, 417. ISBN-13 9789283224327.

5. Carrasco-Garcia, E., Santos, J. C., Garcia, I. & Brianti, M. (2016). Paradoxical role of SOX2 in gastric cancer. Am. J. Cancer Res., 6 (4), 701–13.

6. Cassaro, M., Rugge, M., Tieppo, C., Giacomelli, L., Velo, D. & Farinati, F. (2007). Indefinite for non-invasive neoplasia lesions in gastric intestinal metaplasia: the immunophenotype. J. Clin. Pathol., 60 (6), 615–621.

7. Dixon, M. F., Michael, D. & Path, F. R. C. (1996). Classification and Grading of Gastritis: The Updated Sydney System. Am. J. Surg. Pathol., 20 (10), 1161–1181.

8. Hirata, Y., Maeda, S., Mitsuno, Y., Akanuma, M., Yamaji, Y. & Omata, M. (2001). Helicobacter pylori Activates the Cyclin D1 Gene through Mitogen- Activated Protein Kinase Pathway in Gastric Cancer Cells. Infect Immun., 69 (6). doi:10.1128/IAI.69.6.3965-3971.2001.

9. Ieni, A., Barresi, V., Rigoli, L., Caruso, R. A. & Tuccari, G. (2015). HER2 Status in Premalignant, Early, and Advanced Neoplastic Lesions of the Stomach. Dis. Markers, 234851. doi: 10.1155/2015/234851.

10. Liu, K. C., Lin, B. S., Zhao, M. & Yang, X. (2013). The multiple roles for Sox2 in stem cell maintenance and tumorigenesis. Cell Signal., 25 (5). doi: 10.1016/j.cellsig.2013.02.013.

11. Mutoh, H., Sashikawa, M. & Sugano, K. (2011). Sox2 expression is maintained while gastric phenotype is completely lost in Cdx2-induced intestinal metaplastic mucosa. Differentiation, 81 (2), 92–8. doi: 10.1016/j.diff.2010.10.002.

12. Schlemper, R., Riddell, R. & Kato, Y. (2000). Vienna classification of gastrointestinal epithelial neoplasia. Gut, 47 (2), 251–255.

13. Scholzen, T., Endl, E., Wohlenberg, C., van der Sar, S., Cowell, I. G. & Singh, P. B. (2002). The Ki-67 protein interacts with members of the heterochromatin protein 1 (HP1) family: a potential role in the regulation of higher-order chromatin structure. J. Pathol., 196 (2), 135–144.

14. Sipponen, P. & Maaroos, H. I. (2015). Chronic gastritis. Scand J. Gastroenterol., 50 (6), 657–67. doi: 10.3109/00365521.2015.1019918.

15. Slater, B. (1990). Superiorstain for Helicobacter pylori usingtoluidine. J. Clin. Pathol., 43 (11), 961.

16. Sugai, T., Tsukahara, M., Endoh, M., Shioi, Y. & Takebe, N. (2010). Analysis of cell cycle-related proteins in gastric intramucosal differentiated-type cancers based on mucin phenotypes: a novel hypothesis of early gastric carcinogenesis based on mucin phenotype. BMC Gastroenterol., 10, 55. doi: 10.1186/1471-230X-10-55.

17. Sun, Y., Chen, X. Y., Liu, J., Cheng, X. X., Wang, X. W. & Kong, Q. Y. (2006). Differential caspase-3 expression in noncancerous, premalignant and cancer tissues of stomach and its clinical implication. Cancer Detect Prev., 30 (2), 168–73.

18. van Grieken, N. C., Meijer, G. A., zur Hausen, A., Meuwissen, S. G., Baak, J. P. & Kuipers, E. J. (2003). Increased apoptosis in gastric mucosa adjacent to intestinal metaplasia. Journal of Clinical Pathology, 56 (5), 358–361.

19. Xiao, L. J., Zhao, S., Zhao E-H. & Zheng, X. (2013). Clinicopathological and prognostic significance of Ki-67, caspase-3 and p53 expression in gastric carcinomas. Oncol Lett, 6 (5), 1277–1284. doi:10.3892/ol.2013.1532.

20. Yang, Y., Du, J., Liu, F., Wang, X., Li, X. & Li, Y. (2017). Role of caspase-3/E-cadherin in Helicobacter pylori-induced apoptosis of gastric epithelial cells. Oncotarget., 8 (35), 59204–59216. doi: 10.18632 / oncotarget.19471.

21. Yang, T. T, Cao, N., Zhang, H. H., Wei, J. B. & Song, X. X. (2018). Helicobacter pylori infection-induced H3Ser10 phosphorylation in stepwise gastric carcinogenesis and its clinical implications. Helicobacter, 23 (3). doi: 10.1111/hel.12486.

22. Ying, X., Ying, Y., Ming-xiao, H. & Yun, L. (2015). NaCl pretreatment attenuates H.pylori-induced DNA damage and exacerbates proliferation of gastric epithelial cells (GES-1). Infect Agent Cancer, 10 (8). doi:10.1186/s13027-015-0003-3.
Published
2018-12-28
How to Cite
Sukhan, D., & Vernigorodskiy, S. (2018). Prognostic aspects of immunohistochemical assessment of cellular renewal and transcription factor SOX2 with precancerous changes in the gastric mucosa depending on the genotype of Helicobacter pylori in patients with various types of chronic gastritis. Reports of Vinnytsia National Medical University, 22(4), 674-681. https://doi.org/https://doi.org/10.31393/reports-vnmedical-2018-22(4)-18