Paneth cell adenocarcinoma of the colon: A rare entity

Abdessayed, Nihed; Mrabet, S.; Atika, Baccouche; Ilhem, Ben Jazia; Atef, Ben Abdelkader; Fehmi, Hmila; Mokni, Moncef

doi:10.1016/j.ijscr.2019.10.071

Cited by 3 publications

(3 citation statements)

References 12 publications

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“…In the normal digestive tract, Paneth cells are mainly found in the small intestine. However, in various disease states, they can be abnormally present throughout the digestive tract (99). The presence of Paneth cells in colorectal adenomas was first documented over fifty years ago (100).…”

Section: Expression Of Defa6-icre In Colorectal Tumors and Its Use In...mentioning

confidence: 99%

The fate of secretory cells during intestinal homeostasis, regeneration, and tumor formation is regulated by Tcf4

Janeckova,

Stastna,

Hrckulak

et al. 2024

Preprint

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The single-layer epithelium of the gastrointestinal tract is a dynamically renewing tissue that ensures nutrient absorption, secretory and barrier functions and is involved in immune responses. The basis for this homeostatic renewal is the Wnt signaling pathway. Blocking this pathway can lead to epithelial damage, while its abnormal activation can result in the development of intestinal tumors. In this study, we investigated the dynamics of intestinal epithelial cells and tumorigenesis using a conditional mouse model. Using single-cell and bulk RNA sequencing and histological analysis, we elucidated the cellular responses following the loss of specific cell types. We focused on the fate of cells in the lower parts of the intestinal crypts and the development of colon adenomas. By partially inactivating the transcription factor Tcf4, a key effector of the Wnt signaling pathway, we analyzed the regeneration of isolated hyperproliferative foci (crypts). Our results suggest that the damaged epithelium is not restored by a specific regeneration program associated with oncofetal gene production, but rather by a standard homeostatic renewal pathway. Moreover, disruption of Tcf4 in secretory progenitors resulted in a significant shift in the cell lineage from Paneth cells to goblet cells, characterized by morphological changes and loss of Paneth cell-specific genes. We also found that hyperactivation of the Wnt signaling pathway in colonic adenomas correlated with the upregulation of genes typical of Paneth cells in the intestine, followed by the emergence of secretory tumor cells producing the Wnt3 ligand. The absence of Tcf4 led to a phenotypic shift of the tumor cells towards goblet cells. Our study presents a new model of epithelial regeneration based on the genetically driven partial elimination of intestinal crypts. We highlight the critical role of Tcf4 in the control of cell lineage decisions in the intestinal epithelium and colon tumors.

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Section: Expression Of Defa6-icre In Colorectal Tumors and Its Use In...mentioning

confidence: 99%

The fate of secretory cells during intestinal homeostasis, regeneration, and tumor formation is regulated by Tcf4

Janeckova,

Stastna,

Hrckulak

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Paneth cells are normally found at the bases of the crypts of Lieberkühn in the small intestine 12 . Paneth cells can also be present in low numbers in the proximal colon 10 or throughout the colon as a sign of chronic inflammation in patients with inflammatory bowel disease 15,16 . The granules of Paneth cells consist of several compounds that play a role in immunity and microbial defence.…”

Section: Paneth Cell Metaplasiamentioning

confidence: 99%

“…12 Paneth cells can also be present in low numbers in the proximal colon 10 or throughout the colon as a sign of chronic inflammation in patients with inflammatory bowel disease. 15,16 The granules of Paneth cells consist of several compounds that play a role in immunity and microbial defence. Paneth cells are functionally similar to neutrophils, and release their granules into the crypt lumen via exocytosis when exposed to a variety of stimuli, including acetylcholinergic agonists and bacteria or their antigens.…”

Section: P a T H O P H Y S I O L O G Ymentioning

confidence: 99%

Incidental morphological findings in colorectal adenomas

2020

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Owing to a sharp increase in the frequency of diagnosis of colorectal adenomas in the current era of population screening, distinctive morphological features are increasingly being observed. These may present diagnostic challenges and cause clinical management issues. Paneth cell metaplasia is a more common occurrence, but the incidence rates of squamous metaplasia, clear cell metaplasia, osseous metaplasia, neuroendocrine differentiation and signet‐ring cell‐like lesion are low, and they can be seen in <1% of colorectal adenomas. Their histomorphological characteristics are quite unique; ancillary studies are not very helpful and often not needed. In this review, we give an overview and describe the potential clinical consequences of such incidental and special morphological findings in colorectal adenomas.

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Contribution of Epithelial and Gut Microbiome Inflammatory Biomarkers to the Improvement of Colorectal Cancer Patients’ Stratification

et al. 2022

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In order to ensure that primary endpoints of clinical studies are attained, the patients’ stratification is an important aspect. Selection criteria include age, gender, and also specific biomarkers, such as inflammation scores. These criteria are not sufficient to achieve a straightforward selection, however, in case of multifactorial diseases, with unknown or partially identified mechanisms, occasionally including host factors, and the microbiome. In these cases, the efficacy of interventions is difficult to predict, and as a result, the selection of subjects is often random. Colorectal cancer (CRC) is a highly heterogeneous disease, with variable clinical features, outcomes, and response to therapy; the CRC onset and progress involves multiple sequential steps with accumulation of genetic alterations, namely, mutations, gene amplification, and epigenetic changes. The gut microbes, either eubiotic or dysbiotic, could influence the CRC evolution through a complex and versatile crosstalk with the intestinal and immune cells, permanently changing the tumor microenvironment. There have been significant advances in the development of personalized approaches for CRC screening, treatment, and potential prevention. Advances in molecular techniques bring new criteria for patients’ stratification—mutational analysis at the time of diagnosis to guide treatment, for example. Gut microbiome has emerged as the main trigger of gut mucosal homeostasis. This may impact cancer susceptibility through maintenance of the epithelial/mucus barrier and production of protective metabolites, such as short-chain fatty acids (SCFAs) via interactions with the hosts’ diet and metabolism. Microbiome dysbiosis leads to the enrichment of cancer-promoting bacterial populations, loss of protective populations or maintaining an inflammatory chronic state, all of which contribute to the development and progression of CRC. Meanwhile, variations in patient responses to anti-cancer immuno- and chemotherapies were also linked to inter-individual differences in intestine microbiomes. The authors aim to highlight the contribution of epithelial and gut microbiome inflammatory biomarkers in the improvement of CRC patients’ stratification towards a personalized approach of early diagnosis and treatment.

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Paneth cell adenocarcinoma of the colon: A rare entity

Cited by 3 publications

References 12 publications

The fate of secretory cells during intestinal homeostasis, regeneration, and tumor formation is regulated by Tcf4

The fate of secretory cells during intestinal homeostasis, regeneration, and tumor formation is regulated by Tcf4

Incidental morphological findings in colorectal adenomas

Contribution of Epithelial and Gut Microbiome Inflammatory Biomarkers to the Improvement of Colorectal Cancer Patients’ Stratification

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