title: Identification and characterization of poorly differentiated invasive carcinomas in a mouse model of pancreatic neuroendocrine tumorigenesis.
abstract: Pancreatic neuroendocrine tumors (PanNETs) are a relatively rare but clinically challenging tumor type. In particular, high grade, poorly-differentiated PanNETs have the worst patient prognosis, and the underlying mechanisms of disease are poorly understood. In this study we have identified and characterized a previously undescribed class of poorly differentiated PanNETs in the RIP1-Tag2 mouse model. We found that while the majority of tumors in the RIP1-Tag2 model are well-differentiated insulinomas, a subset of tumors had lost multiple markers of beta-cell differentiation and were highly invasive, leading us to term them poorly differentiated invasive carcinomas (PDICs). In addition, we found that these tumors exhibited a high mitotic index, resembling poorly differentiated (PD)-PanNETs in human patients. Interestingly, we identified expression of Id1, an inhibitor of DNA binding gene, and a regulator of differentiation, specifically in PDIC tumor cells by histological analysis. The identification of PDICs in this mouse model provides a unique opportunity to study the pathology and molecular characteristics of PD-PanNETs.
authors.affiliation: Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Hunter
authors.forename: Marsha L
authors.initials: ML
authors.lastname: Quick
authors.forename: Anguraj
authors.initials: A
authors.lastname: Sadanandam
authors.forename: Douglas
authors.initials: D
authors.lastname: Hanahan
authors.forename: Johanna A
authors.initials: JA
authors.lastname: Joyce
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D063646:Carcinogenesis; D018278:Carcinoma, Neuroendocrine / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics; D051379:Mice; D008938:Mitosis; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; C497455:Idb1 protein, mouse; D051798:Inhibitor of Differentiation Protein 1