How does intestinal-type intraductal papillary mucinous neoplasm emerge? CDX2 plays a critical role in the process of intestinal differentiation and progression

Omori, Yuko; Ono, Yoshio; Kobayashi, Toshikatsu; Motoi, Fuyuhiko; Karasaki, Hidenori; Mizukami, Yusuke; Makino, Naohiko; Ueno, Yoshiyuki; Unno, Michiaki; Furukawa, Toru

doi:10.1007/s00428-020-02806-8

Cited by 20 publications

(22 citation statements)

References 29 publications

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“…Furthermore, the GNAS signal does not seem sufficient to initiate the differentiation toward the intestinal pathway. In a recent study including 60 intestinal-type IPMN specimens, Omori et al [85] observed a histological transition from gastric-type epithelia to intestinal-type epithelia in 48 cases (80%). This transition was driven by CDX2, which expression seems to precede the acquisition of intestinal features and MUC2 expression [85].…”

Section: Murine Models Of Ipmn Initiationmentioning

confidence: 97%

“…In a recent study including 60 intestinal-type IPMN specimens, Omori et al [85] observed a histological transition from gastric-type epithelia to intestinal-type epithelia in 48 cases (80%). This transition was driven by CDX2, which expression seems to precede the acquisition of intestinal features and MUC2 expression [85]. The authors suggested that intestinal type IPMNs might develop from gastric-type lesions after induction of CDX2, which could be related to the GNAS signaling and additional molecular events including RNF43 and ß-catenin.…”

Section: Murine Models Of Ipmn Initiationmentioning

confidence: 97%

“…The RNF43 mutations might represent a later event as found mainly in high-grade lesions (20-75% versus 0-10% in low-grade IPMNs) [66,83]. Moreover, they are also significantly associated with GNAS mutations and the intestinal subtype, suggesting a synergistic role of these two events, particularly in the progression of the intestinal pathway [69,70,84,85]. However, RNF43 mutations might be involved mainly in the low grade-high grade transition since these alterations does not seem to be selected during progression to an invasive carcinoma [86,87].…”

Section: Other Mutationsmentioning

confidence: 99%

“…(80%). This transition was driven by CDX2, which expression seems to precede the acquisition of intestinal features and MUC2 expression [85]. The authors suggested that intestinal type IPMNs might develop from gastric-type lesions after induction of CDX2, which could be related to the GNAS signaling and additional molecular events including RNF43 and ß-catenin.…”

Section: Murine Models Of Ipmn Initiationmentioning

confidence: 99%

See 3 more Smart Citations

Intraductal Papillary Mucinous Carcinoma Versus Conventional Pancreatic Ductal Adenocarcinoma: A Comprehensive Review of Clinical-Pathological Features, Outcomes, and Molecular Insights

Mas

Lupinacci

Cros

et al. 2021

IJMS

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Intraductal papillary mucinous neoplasms (IPMN) are common and one of the main precursor lesions of pancreatic ductal adenocarcinoma (PDAC). PDAC derived from an IPMN is called intraductal papillary mucinous carcinoma (IPMC) and defines a subgroup of patients with ill-defined specificities. As compared to conventional PDAC, IPMCs have been associated to clinical particularities and favorable pathological features, as well as debated outcomes. However, IPMNs and IPMCs include distinct subtypes of precursor (gastric, pancreato-biliary, intestinal) and invasive (tubular, colloid) lesions, also associated to specific characteristics. Notably, consistent data have shown intestinal IPMNs and associated colloid carcinomas, defining the “intestinal pathway”, to be associated with less aggressive features. Genomic specificities have also been uncovered, such as mutations of the GNAS gene, and recent data provide more insights into the mechanisms involved in IPMCs carcinogenesis. This review synthetizes available data on clinical-pathological features and outcomes associated with IPMCs and their subtypes. We also describe known genomic hallmarks of these lesions and summarize the latest data about molecular processes involved in IPMNs initiation and progression to IPMCs. Finally, potential implications for clinical practice and future research strategies are discussed.

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Section: Murine Models Of Ipmn Initiationmentioning

confidence: 97%

Section: Murine Models Of Ipmn Initiationmentioning

confidence: 97%

Section: Other Mutationsmentioning

confidence: 99%

Section: Murine Models Of Ipmn Initiationmentioning

confidence: 99%

See 2 more Smart Citations

Intraductal Papillary Mucinous Carcinoma Versus Conventional Pancreatic Ductal Adenocarcinoma: A Comprehensive Review of Clinical-Pathological Features, Outcomes, and Molecular Insights

Mas

Lupinacci

Cros

et al. 2021

IJMS

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“…9 The expression of CDX2 in gastric-type IPMN suggests that CDX2 precedes the expression of MUC2 and maturation of intestinal features. 10 However, no information regarding the precise role of CDX2 expression during the tumor progression of intestinal-type IPMN has been reported. Furthermore, whether the systemic mechanism underlying the intestinal differentiation is reflected in intestinal-type IPMN remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Intestinal phenotype is maintained by Atoh1 in the cancer region of intraductal papillary mucinous neoplasm

et al. 2020

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Intraductal papillary mucinous neoplasm (IPMN) is a precancerous lesion of pancreatic cancer. Although there are 4 types of IPMN, among which intestinal‐type IPMN is likely to progress into invasive cancer known as colloid carcinoma, no information regarding the involvement of the intestinal phenotype in the carcinogenesis of IPMN exists. The present study was conducted to explore how the intestinal differentiation system is maintained during the tumor progression of intestinal‐type IPMN using surgical resection specimens. Results showed that Atoh1, a critical transcriptional factor for intestinal differentiation toward the secretory lineages of intestinal epithelial cells, was expressed in an invasive‐grade IPMN. To determine the function of Atoh1 in pancreatic cancer, we generated a pancreatic ductal adenocarcinoma (PDAC) cell line overexpressing Atoh1. In a xenograft model, we successfully induced an IPMN phenotype in PDAC cells via Atoh1 induction. Finally, for the first time, we discovered that GPA33 is expressed in intestinal‐type IPMN, thereby suggesting a novel target for cancer therapy. In conclusion, the intestinal differentiation system might be maintained during tumor progression of intestinal‐type IPMN. Further analysis of the function of Atoh1 in IPMN might be useful for understanding the molecular mechanism underlying the malignant potential during the tumor progression of IPMN.

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Pancreatic Cancer

2023

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How does intestinal-type intraductal papillary mucinous neoplasm emerge? CDX2 plays a critical role in the process of intestinal differentiation and progression

Cited by 20 publications

References 29 publications

Intraductal Papillary Mucinous Carcinoma Versus Conventional Pancreatic Ductal Adenocarcinoma: A Comprehensive Review of Clinical-Pathological Features, Outcomes, and Molecular Insights

Intraductal Papillary Mucinous Carcinoma Versus Conventional Pancreatic Ductal Adenocarcinoma: A Comprehensive Review of Clinical-Pathological Features, Outcomes, and Molecular Insights

Intestinal phenotype is maintained by Atoh1 in the cancer region of intraductal papillary mucinous neoplasm

Pancreatic Cancer

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