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The Association Between Inflammation, Epithelial Mesenchymal Transition and Stemness in Colorectal Carcinoma

Authors Briede I, Strumfa I, Vanags A, Gardovskis J

Received 24 July 2019

Accepted for publication 11 November 2019

Published 8 January 2020 Volume 2020:13 Pages 15—34

DOI https://doi.org/10.2147/JIR.S224441

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Ning Quan


Inese Briede,1 Ilze Strumfa,1 Andrejs Vanags,2 Janis Gardovskis2

1Department of Pathology, Riga Stradins University, Riga, Latvia; 2Department of Surgery, Riga Stradins University, Riga, Latvia

Correspondence: Inese Briede
Department of Pathology, Riga Stradins University, 9A Kuldigas Street, Riga LV-1007, Latvia
Tel +371 67815096
Fax +371 67471815
Email Inese.Briede@rsu.lv

Background: Inflammation plays an important albeit dual role in carcinogenesis. Survival studies have highlighted the prognostic significance of peritumorous inflammation. Currently, the theoretical background allows inflammation, epithelial mesenchymal transition (EMT) and the closely associated stem cell differentiation in colorectal carcinoma (CRC) to be linked. However, there is scarce direct morphological evidence.
Purpose and methods: The aim of our study was to investigate the role of inflammation in cancer growth and invasion by analyzing the association between inflammation and known morphological prognostic features of colorectal cancer, EMT, stemness and mismatch repair (MMR) protein expression. The study was designed as a retrospective morphological and immunohistochemical assessment of 553 consecutive cases of surgically treated primary CRC.
Results: There were statistically significant associations between high-grade inflammation and lower pT (p = 0.002), absence of lymph node metastases (p < 0.001) and less frequent lymphatic (p = 0.003), venous (p = 0.017), arterial (p = 0.012), perineural (p = 0.001) and intraneural (p = 0.01) invasion. In contrast, Crohn’s like reaction (CLR) by density of lymphoid follicles in the invasive front lacked significant differences in regard to pT, pN, tumor invasion into surrounding structures (blood or lymphatic vessels, nerves), grade or necrosis (all p > 0.05). The expression of E-cadherin, CD44 and MMR proteins yielded no statistically significant associations with peritumorous inflammation by Klintrup-Mäkinen score or the density of lymphoid follicles. Nevertheless, E-cadherin levels were significantly associated with the density of eosinophils (p = 0.007).
Conclusion: High-grade peritumorous inflammation is associated with beneficial morphologic CRC features, including less frequent manifestations of invasion, and is not secondary to tissue damage and necrosis. CLR is not associated with cancer spread by pTN; this finding indirectly suggests an independent role of CLR in carcinogenesis. Further, inflammation by Klintrup-Mäkinen grade and CLR is not dependent on epithelial-mesenchymal transition and stem cell differentiation. Our study highlights the complex associations between inflammation, tumor morphology, EMT, stemness and MMR protein expression in human CRC tissues.

Keywords: colorectal carcinoma, inflammation, Klintrup-Mäkinen score, immunohistochemistry, CD44, mismatch repair proteins

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