Inflammation – the microenvironment for tumor progression and stem cell differentiation in colorectal carcinoma

Colorectal carcinogenesis shows intricate links with epithelial-mesenchymal transition (EMT) and inflammation. Down-regulation of E-cadherin (EC) is associated with cancer progression [Christou et al.,2017] while over-expression of N-cadherin (NC) has been linked to decreased survival [Xuebing et al.,2015] in colorectal carcinoma (CRC). The study included 553 consecutive retrospective CRC cases, subjected to microscopic evaluation including assessment of inflammation. To study the hypothetical relation between EMT, tumor stemness and inflammation, immunohistochemistry for EC, NC and CD44 was performed. Statistical analysis was done. Adenocarcinoma was found in 88.8% [95% confidence interval: 85.9–91.2], mucinous CRC in 9.6% [7.4–12.3] and primary colorectal signet ring cell carcinoma in 1.2% [0.6–2.6] of cases. By pT, locally advanced tumors predominated: pT3 carcinoma represented 49.6% [45.4–53.7] and pT4 – 35.6% [31.7–39.7]. By grade (G), G2 cancers constituted 64.0% [59.9–67.9], and G3 carcinoma – 25.7% [22.2–29.5] of CRCs. Low-grade inflammation according to the Klintrup-Mäkinen score was observed in 292 (52.8% [48.6–56.9]) tumours and high-grade inflammation – in 261 (47.2% [43.1–51.4]) carcinomas. There were statistically significant differences regarding pT distribution (p=0.002) and status of regional lymph nodes pN (p<0.001) in relation to low- and high-grade inflammation. The overall EC score was 1.86[1.78–1.94]; CD44 1.33[1.20–1.46]; N-cadherin 1.76[1.57-1.95]. There was statistically significant differences in EC and CD44 score regarding tumor histogenesis (p<0.01). NC levels differed only regarding pT (p<0.05). In contrast, CD44 levels did not vary by pT, grade or manifestations of invasive growth. The expression of EC showed statistically significant differences by grade (p<0.01). As regards inflammation and EMT, the only significant finding was the association between high density of eosinophils and upregulation of EC (p<0.01). Peritumorous inflammation is associated with local and metastatic tumour spread. EMT has a role on a tumor progression, but there is no evidence to its relation with an inflammation.