Identification and characterization of poorly differentiated invasive carcinomas in a mouse model of pancreatic neuroendocrine tumorigenesis

PLoS One. 2013 May 14;8(5):e64472. doi: 10.1371/journal.pone.0064472. Print 2013.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism
  • Carcinogenesis*
  • Carcinoma, Neuroendocrine / genetics
  • Carcinoma, Neuroendocrine / metabolism
  • Carcinoma, Neuroendocrine / pathology*
  • Disease Models, Animal*
  • Gene Expression Regulation, Neoplastic
  • Inhibitor of Differentiation Protein 1 / genetics
  • Mice
  • Mitosis
  • Neoplasm Invasiveness
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*

Substances

  • Biomarkers, Tumor
  • Idb1 protein, mouse
  • Inhibitor of Differentiation Protein 1