Detection of Precursor Lesions of Pancreatic Adenocarcinoma in PET-CT in a Genetically Engineered Mouse Model of Pancreatic Cancer
Background: Pancreatic cancer is among the most dismal of human malignancies. The 5-year survival rate is lower than 5%. The identification of precursor lesions would be the main step to improve this fatal outcome. One precursor lesions are called pancreatic intraepithelial neoplasia (PanIN) and ar...
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doaj-868592bff59f4467b28a5641761c9d312020-11-24T20:58:44ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022011-02-0113218018610.1593/neo.10956Detection of Precursor Lesions of Pancreatic Adenocarcinoma in PET-CT in a Genetically Engineered Mouse Model of Pancreatic CancerVolker Fendrich0Ralph Schneider1Anirban Maitra2Ilse D. Jacobsen3Thomas Opfermann4Detlef K. Bartsch5Department of Surgery, Philipps University Marburg, Marburg, GermanyDepartment of Surgery, Philipps University Marburg, Marburg, GermanyDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USADepartment of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, GermanyDepartment of Cell and Molecular Biology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, GermanyDepartment of Surgery, Philipps University Marburg, Marburg, Germany Background: Pancreatic cancer is among the most dismal of human malignancies. The 5-year survival rate is lower than 5%. The identification of precursor lesions would be the main step to improve this fatal outcome. One precursor lesions are called pancreatic intraepithelial neoplasia (PanIN) and are graduated in grade 1 to 3, whereas grade 3 is classified as carcinoma in situ. Currently, no reliable, noninvasive imaging technique (e.g., ultrasound, computed tomography, magnet resonance imaging) exists to verify PanINs. Methods: Recently, a transgenic mouse model of pancreatic cancer was established in which the tumor progression of human pancreatic carcinoma is reproduced. These so-called Pdx-1-Cre; LSL-KrasG12D/+; LSL-Trp53R172H/+mice develop PanINs, which transform to invasive growing pancreatic carcinoma. The pancreata of mice of different ages were immunohistochemically stained using α-GLUT-2 antibodies. Furthermore, mice underwent positron emission tomography (PET)-computed tomography (CT) with 18F-fluorodeoxyglucose (FDG) to evaluate early detection of PanIN lesions. Results: An expression of GLUT-2 in murine PanINs was found in PanINs of grade 1B and higher. This finding is associated with an elevated glucose metabolism, leading to the detection of precursor lesions of pancreatic cancer in the FDG PET-CT scan. In addition, immunohistochemical staining of GLUT-2 was detectable in 45 (75%) of 60 human PanINs, whereas PanINs of grade 1B and higher showed a very extensive expression. Conclusions: In conclusion, we demonstrate for the first time that an elevated glucose metabolism occurs already in precursor lesions of murine and human pancreatic carcinoma. These findings are the basis for the detection of precursor lesions by PET-CT, thereby helping improving the prognosis of this devastating disease. http://www.sciencedirect.com/science/article/pii/S1476558611800564 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Volker Fendrich Ralph Schneider Anirban Maitra Ilse D. Jacobsen Thomas Opfermann Detlef K. Bartsch |
spellingShingle |
Volker Fendrich Ralph Schneider Anirban Maitra Ilse D. Jacobsen Thomas Opfermann Detlef K. Bartsch Detection of Precursor Lesions of Pancreatic Adenocarcinoma in PET-CT in a Genetically Engineered Mouse Model of Pancreatic Cancer Neoplasia: An International Journal for Oncology Research |
author_facet |
Volker Fendrich Ralph Schneider Anirban Maitra Ilse D. Jacobsen Thomas Opfermann Detlef K. Bartsch |
author_sort |
Volker Fendrich |
title |
Detection of Precursor Lesions of Pancreatic Adenocarcinoma in PET-CT in a Genetically Engineered Mouse Model of Pancreatic Cancer |
title_short |
Detection of Precursor Lesions of Pancreatic Adenocarcinoma in PET-CT in a Genetically Engineered Mouse Model of Pancreatic Cancer |
title_full |
Detection of Precursor Lesions of Pancreatic Adenocarcinoma in PET-CT in a Genetically Engineered Mouse Model of Pancreatic Cancer |
title_fullStr |
Detection of Precursor Lesions of Pancreatic Adenocarcinoma in PET-CT in a Genetically Engineered Mouse Model of Pancreatic Cancer |
title_full_unstemmed |
Detection of Precursor Lesions of Pancreatic Adenocarcinoma in PET-CT in a Genetically Engineered Mouse Model of Pancreatic Cancer |
title_sort |
detection of precursor lesions of pancreatic adenocarcinoma in pet-ct in a genetically engineered mouse model of pancreatic cancer |
publisher |
Elsevier |
series |
Neoplasia: An International Journal for Oncology Research |
issn |
1476-5586 1522-8002 |
publishDate |
2011-02-01 |
description |
Background: Pancreatic cancer is among the most dismal of human malignancies. The 5-year survival rate is lower than 5%. The identification of precursor lesions would be the main step to improve this fatal outcome. One precursor lesions are called pancreatic intraepithelial neoplasia (PanIN) and are graduated in grade 1 to 3, whereas grade 3 is classified as carcinoma in situ. Currently, no reliable, noninvasive imaging technique (e.g., ultrasound, computed tomography, magnet resonance imaging) exists to verify PanINs. Methods: Recently, a transgenic mouse model of pancreatic cancer was established in which the tumor progression of human pancreatic carcinoma is reproduced. These so-called Pdx-1-Cre; LSL-KrasG12D/+; LSL-Trp53R172H/+mice develop PanINs, which transform to invasive growing pancreatic carcinoma. The pancreata of mice of different ages were immunohistochemically stained using α-GLUT-2 antibodies. Furthermore, mice underwent positron emission tomography (PET)-computed tomography (CT) with 18F-fluorodeoxyglucose (FDG) to evaluate early detection of PanIN lesions. Results: An expression of GLUT-2 in murine PanINs was found in PanINs of grade 1B and higher. This finding is associated with an elevated glucose metabolism, leading to the detection of precursor lesions of pancreatic cancer in the FDG PET-CT scan. In addition, immunohistochemical staining of GLUT-2 was detectable in 45 (75%) of 60 human PanINs, whereas PanINs of grade 1B and higher showed a very extensive expression. Conclusions: In conclusion, we demonstrate for the first time that an elevated glucose metabolism occurs already in precursor lesions of murine and human pancreatic carcinoma. These findings are the basis for the detection of precursor lesions by PET-CT, thereby helping improving the prognosis of this devastating disease.
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url |
http://www.sciencedirect.com/science/article/pii/S1476558611800564 |
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