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. 2018 Oct 4:2018:6578273.
doi: 10.1155/2018/6578273. eCollection 2018.

Diverse Expression of IL-32 in Diffuse and Intestinal Types of Gastric Cancer

Mladen Pavlovic  1 , Nevena Gajovic  2 , Milena Jurisevic  3 , Slobodanka Mitrovic  4 , Gordana Radosavljevic  2 , Jelena Pantic  2 , Nebojsa Arsenijevic  2 , Ivan Jovanovic  2
Affiliations

Diverse Expression of IL-32 in Diffuse and Intestinal Types of Gastric Cancer

Mladen Pavlovic et al. Gastroenterol Res Pract. .

Abstract

Introduction: Gastric cancer (GC) represents one of the most common cancers worldwide, frequently diagnosed at advanced stages with poor prognosis, indicating on need for new diagnostic and prognostic markers. The aim of the study was to determine the expression of IL-32, proinflammatory and angiogenic mediators, in patients with diffuse and intestinal gastric cancer and the relationship with clinicopathological aspects.

Material and methods: The tissue samples of diffuse and intestinal types of tumor of 70 patients with gastric cancer were analyzed. Expression of IL-32, VEGF, IL-17, and CD31 was measured by immunohistochemistry.

Results: IL-32 expression was significantly lower in tissue samples from patients with diffuse type of gastric cancer that is also a severe and more progressive form (TNM stages III and IV, poor histological differentiation, and higher nuclear grade III). Expression of IL-17 was also decreased in patients with diffuse type of gastric cancer. Microvascular density was diminished in diffuse type of gastric cancer.

Conclusions: Downregulated expression of IL-32 in tumor tissue of patients with diffuse type of gastric cancer may implicate on its role in limiting ongoing proinflammatory and proangiogenic processes. This emphasizes on unrecognized role of IL-32 in biology of diffuse type of gastric cancer.

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Figures

Figure 1
Figure 1
IL-32 score in patients with intestinal and diffuse form of gastric cancer. (a) Patients with diffuse type of cancer had IL-32 score 4 or less, while patients with intestinal type had IL-32 score 4 or higher. Significantly lower IL-32 score in patients with diffuse type in comparison to patients with intestinal type of gastric cancer (p = 0.001). p values were assessed by Student's unpaired t-test. (b). H&E staining of representative tumor tissue of intestinal and diffuse type of gastric cancer. Representative IL-32 staining in patients with intestinal and diffuse type of gastric cancer (200 and 400x magnification).
Figure 2
Figure 2
Microvascular density of intestinal and diffuse form of gastric cancer. (a) MVD was significantly lower in patients with diffuse form compared to patients with intestinal form of gastric cancer (p = 0.009). p values were assessed by Mann–Whitney rank sum test. (b) H&E staining of representative tumor tissue of intestinal and diffuse type of gastric cancer. Representative sections demonstrate MVD in tumor tissue of patients with intestinal and diffuse type of gastric cancer (200 and 400x magnification).
Figure 3
Figure 3
Immunohistochemical analysis of IL-17 and VEGF in patients with intestinal and diffuse form of gastric cancer. (a) Significantly lower IL-17 score in patients with diffuse type in comparison to patients with intestinal type of gastric cancer (p = 0.029). (b) No statistical significance in VEGF score between patients with diffuse form and intestinal form of gastric cancer (p > 0.05). p values were assessed by Mann–Whitney rank sum test. (c) Representative IL-17 and VEGF staining in tumor tissue of patients with intestinal and diffuse type of gastric cancer (200 and 400x magnification).
Figure 4
Figure 4
Schematic diagram describing mechanism responsible for IL-32-mediated suppression of angiogenesis in diffuse type of gastric cancer. IL-32 directly and indirectly, through the suppression of IL-17, reduces angiogenesis and subsequent microvascular density, which in turn attenuates hematogenous metastasis of diffuse type of gastric cancer.
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