Predictive potential of macrophage population phenotyping in malignization of H. pylori-associated chronic gastritis

Golubinskaya EP1, Sataieva TP1, Fomochkina II1, Kubyshkin AV1, Makalish TP1, Shkolyar NA2, Galyshevskaya AA1, Varghese DV1
About authors

1 V.I. Vernadsky Crimean Federal University, Simferopol, Russia

2 Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia

Correspondence should be addressed: Tatiana P. Sataieva
Bulvar Lenina, 5/7, Simferopol, 295006; ur.liam@loocznat

About paper

Funding: the study was carried out within the framework of the Government Assignment № FZEG-2020-0060 of the Ministry of Science and Higher Education of the Russian Federation in the field of scientific research “Algorithms for molecular genetic diagnosis of malignant neoplasms and approaches to their targeted therapy using cellular and genetic technologies”.

Author contribution: Golubinskaya EP — clinical data analysis, immunohistochemistry, manuscript editing; Sataieva TP, Fomochkina II — systematic analysis, manuscript writing; Kubyshkin AV — statistical analysis, manuscript editing; Makalish TP — sample preparation for morphological assessment, immunohistochemistry; Shkolyar NA — biopsy sample collection and preparation; Galyshevskaya AA, Varghese DV — morphometric data processing.

Compliance with ethical standards: the study was approved by the Ethics Committee of the Medical Academy named after S. I. Georgievsky (protocol № 15 dated December 5, 2020); the study was conducted in accordance with the Declaration of Helsinki 1964 (revised in 1975 and 1983), Good Clinical Practice (GCP) standards and the Federal Law № 323-FZ “On the Basics of Protecting the Health of Citizens in the Russian Federation” dated November 21, 2011. The informed consent was submitted by all patients.

Received: 2021-08-19 Accepted: 2021-08-03 Published online: 2021-09-14

Tumor-associated macrophages are able to regulate the tumor cell proliferation and to affect the tumor cell dissemination. The study was aimed to assess the predictive potential of the macrophage population immunohistochemical phenotyping in early malignization of H. pylori-associated chronic gastritis. Gastic biopsy samples of male and female patients aged 48 ± 7.2 infected with Helicobacter pylori were used as the research material. The patients were divided into three groups: non-atrophic chronic gastritis (NACG, n = 10), atrophic chronic gastritis (ACG, n = 10), G1/G2 gastric adenocarcinoma (GAC, n = 10). The macrophage population was visualized using the CD68 pan-macrophage marker and the type 2 monocyte/macrophage marker CD163. Intensity of neoangiogenesis was defined using the CD31 endothelial marker by assessing the total cross sectional area of blood vessels. It was found that chronic gastritis was accompanied by the dynamic increase in the size of the general macrophage population with the progression of atrophic and metaplastic processes. According to immunohistochemical study of biopsies obtained from patients with NCG, the CD163 : CD68 ratio was 0.67 ± 0.02, and the total cross sectional area of blood vessels was 3590.92 ± 356.27 µm2. Atrophic gastritis and adenocarcinoma were characterized by vector redistribution of monocytes/macrophages into the 2nd functional phenotype. The CD163 : CD68 expression index in the group with ACG was 0.81 ± 0.04, and in the group with GAC it was 0.88 ± 0.03. Microvascular area was significantly increased in the groups with ACG and GAC, which reflected tumor neoangiogenesis intensification under the influence of М2 monocytes/macrophages. The increased expression of CD163 can serve as a predictor of chronic gastritis malignization together with evaluation of the glandular epithelium atrophy and metaplasia degree.

Keywords: adenocarcinoma, gastric cancer, gastritis, tumor-associated macrophages, Helicobacter pylori