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

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, LatviaCorrespondence: Inese BriedeDepartment of Pathology, Riga Stradins University, 9A Kuldigas Street, Riga LV-...

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Autores principales:	Briede I, Strumfa I, Vanags A, Gardovskis J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	colorectal carcinoma inflammation klintrup-mäkinen score immunohistochemistry cd44 mismatch repair proteins Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/47f4134d19a8419983f4f6a632105db2
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spelling	oai:doaj.org-article:47f4134d19a8419983f4f6a632105db22021-12-02T11:26:28ZThe Association Between Inflammation, Epithelial Mesenchymal Transition and Stemness in Colorectal Carcinoma1178-7031https://doaj.org/article/47f4134d19a8419983f4f6a632105db22020-01-01T00:00:00Zhttps://www.dovepress.com/the-association-between-inflammation-epithelial-mesenchymal-transition-peer-reviewed-article-JIRhttps://doaj.org/toc/1178-7031Inese 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, LatviaCorrespondence: Inese BriedeDepartment of Pathology, Riga Stradins University, 9A Kuldigas Street, Riga LV-1007, LatviaTel +371 67815096Fax +371 67471815Email Inese.Briede@rsu.lvBackground: 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 proteinsBriede IStrumfa IVanags AGardovskis JDove Medical Pressarticlecolorectal carcinomainflammationklintrup-mäkinen scoreimmunohistochemistrycd44mismatch repair proteinsPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 13, Pp 15-34 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	colorectal carcinoma inflammation klintrup-mäkinen score immunohistochemistry cd44 mismatch repair proteins Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	colorectal carcinoma inflammation klintrup-mäkinen score immunohistochemistry cd44 mismatch repair proteins Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Briede I Strumfa I Vanags A Gardovskis J The Association Between Inflammation, Epithelial Mesenchymal Transition and Stemness in Colorectal Carcinoma
description	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, LatviaCorrespondence: Inese BriedeDepartment of Pathology, Riga Stradins University, 9A Kuldigas Street, Riga LV-1007, LatviaTel +371 67815096Fax +371 67471815Email Inese.Briede@rsu.lvBackground: 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
format	article
author	Briede I Strumfa I Vanags A Gardovskis J
author_facet	Briede I Strumfa I Vanags A Gardovskis J
author_sort	Briede I
title	The Association Between Inflammation, Epithelial Mesenchymal Transition and Stemness in Colorectal Carcinoma
title_short	The Association Between Inflammation, Epithelial Mesenchymal Transition and Stemness in Colorectal Carcinoma
title_full	The Association Between Inflammation, Epithelial Mesenchymal Transition and Stemness in Colorectal Carcinoma
title_fullStr	The Association Between Inflammation, Epithelial Mesenchymal Transition and Stemness in Colorectal Carcinoma
title_full_unstemmed	The Association Between Inflammation, Epithelial Mesenchymal Transition and Stemness in Colorectal Carcinoma
title_sort	association between inflammation, epithelial mesenchymal transition and stemness in colorectal carcinoma
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/47f4134d19a8419983f4f6a632105db2
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The Association Between Inflammation, Epithelial Mesenchymal Transition and Stemness in Colorectal Carcinoma

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