Immunohistochemical evaluation of IL-6 expression level andIL-6/STAT3/hMSH3 pathway in colorectal adenocarcinomas

Colorectal cancer is the most common type of gastrointestinal cancer, and its incidence is increasing worldwide due to changes in lifestyle. While only a minority of colorectal carcinomas develop due to hereditary causes, the majority are due to non-hereditary, environmental factors. Among these reasons, chronic inflammation has a rare but important place in etiology. Inflammation is thought to play a role in the pathogenesis of carcinoma in patients who do not have a clinical diagnosis of inflammatory bowel disease and show no symptoms. In recent years, the pathogenesis of colorectal adenocarcinoma is classified according to similar morphological, molecular and clinical features. Instead of being explained with a single adenoma-carcinoma sequence, molecular heterogenity comes to the fore in pathogenesis. A form of microsatellite changes is "Elevated Microsatellite Alterations at Selected Tetranucleotide Repeats"- EMAST is reported in 60% of colon carcinomas and 33% of rectal carcinomas. There are studies showing that IL-6 and oxidative stress cause cytosolic shift of MSH3 and cause EMAST tumors. Some immunological and inflammatory responses are thought to play a role in the pathogenesis of EMAST tumors. 64 Although our cases frequently demonstrated increased expression of IL-6 and loss of MSH3 nuclear expression, it has not been proven that increased expression of IL-6 causes loss of nuclear staining of MSH3. Other mechanisms that could explain the loss of MSH3 can be considered here. MSH3 staining was found to be significantly less in patients with high immune response to the tumor compared to the other groups. Whether MSH3 can determine the EMAST status is controversial. If such a relationship is demonstrated, the loss of MSH3 in cases with high tumor infiltrating lymphocytes may contribute to the fact that we have shown that EMAST positive tumors have an excessive immune response. Also it is thought that determination of IL-6 expression by immunohistochemistry may be important in patient selection for anti-IL6 therapies in the future.