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Updated: May 13, 2026
08:54
An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells
Published on: July 20, 2014
Insulin/Insulin-Like Growth Factor-1 Pathway in Barrett's Carcinogenesis
K B Greer1, A Kresak, B Bednarchik
1Division of Gastroenterology and Liver Disease, University Hospitals of Cleveland, Cleveland, Ohio, USA.
Clinical and Translational Gastroenterology
|March 8, 2013
Summary
Activation of the insulin/IGF-1 pathway in Barrett's esophagus (BE) correlates with increased cellular proliferation and progression to esophageal adenocarcinoma (EAC). Tissue-level pathway activation is complex and not directly linked to systemic insulin or IGF-1 levels.
Area of Science:
- Gastroenterology
- Oncology
- Endocrinology
Background:
- Obesity is linked to increased cancer risk, potentially via insulin and insulin-like growth factor (IGF) signaling.
- The insulin/IGF-1 pathway's role in esophageal carcinogenesis, from metaplasia to adenocarcinoma, requires further elucidation.
Purpose of the Study:
- To investigate the involvement of the insulin/IGF-1 pathway in the progression of Barrett's esophagus (BE) to dysplasia and esophageal adenocarcinoma (EAC).
Main Methods:
- Measured fasting serum levels of insulin, glucose, IGF-1, IGFBP1, and IGFBP3 in subjects with BE, low-grade dysplasia (LGD), high-grade dysplasia (HGD), and EAC.
- Utilized immunohistochemistry on BE tissue to assess markers of pathway activation: p-mammalian target of rapamycin (mTOR), p-AKT, Ki-67, and p-insulin receptor substrate 1 (IRS1).
Main Results:
- Strong p-IRS1 staining increased progressively from BE (43.2%) to LGD (55%), HGD (66.7%), and EAC (70%).
- HGD/EAC subjects showed significantly higher p-IRS1 staining compared to BE/LGD subjects (63.6% vs. 41.5%, P<0.05).
- p-IRS1 staining moderately correlated with downstream mediators (p-AKT, p-mTOR) and proliferation marker Ki-67, but not with systemic insulin or IGF-1 levels.
Conclusions:
- Activation of the insulin/IGF-1 pathway in BE tissue is associated with cellular proliferation and may play a role in esophageal cancer progression.
- Tissue-level insulin/IGF-1 pathway activation is complex and not simply explained by systemic hormone levels.
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