Abstract
Proinflammatory counterworks are important at different stages of tumor development, particularly during invasion and metastasis. Immune cells and their signal molecules can influence all stages of tumor progression, as well as therapeutic intervention. Proinflammatory cytokines are known triggers of growth in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). In this study, we explored the immunohistochemical expression of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), IL-2, and IL-6 in tissues from 43 GEP-NEN patients with tumors of gastric, duodenal, ileal, appendiceal, and colonic origin. The immunohistochemical expression of TNF-α was increased in tumor groups with high proliferation rates (Ki-67; p = 0.034), as well as in those with higher tumor grades (p = 0.05). Moreover, the immunohistochemical expression of TNF-α positively correlated with death outcomes (p = 0.016). Expression of IL-6, IL-1β, and IL-2 displayed similar immunohistochemical expression patterns regardless of Ki-67, although the expression between the ILs differed. Most GEP-NENs had high levels of IL-6 and lower levels of IL-1β and IL-2. Although further comprehensive studies are required for a complete understanding of activated mechanisms in proinflammatory protumoral microenvironment of GEP-NENs, TNF-α is a potential marker in the prognosis of those tumors.
Highlights
Inflammation is one of the mechanisms involved in creating protumoral microenvironments in many different organs, in particular, in the gastrointestinal tract
Most GEP-NENs displayed high expression of IL-6 and reduced expression of IL-1β and Nowadays, it is generally accepted that proinflammatory microenvironments are important drivers of all tumors; substantial efforts have been devoted to the biochemical and immunological cytokine network interactions that promote the progression of tumors
Several multicenter studies have demonstrated that the presence of various polymorphisms in genes coding for ILs, such as IL-1, IL-6, and/or IL-8, is strongly associated with increased risks of cancer development [11,12]
Summary
Inflammation is one of the mechanisms involved in creating protumoral microenvironments in many different organs, in particular, in the gastrointestinal tract. They have an important role in regulating inflammatory cells, especially macrophages, to create protumoral microenvironments during chronic inflammation and provide the tumor with the ability to evade host responses. Little is known about the potential diagnostic or clinical value of measuring systemic cytokine levels in patients with different types of neuroendocrine tumors or their value as diagnostic or prognostic indicators for pathohistological evaluations.
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