Expression of estrogen-induced genes and estrogen receptor ? in pancreatic neuroendocrine tumors: implications for targeted therapy.

ABSTRACT: The indolent nature and expression of progesterone receptor (PR), a well-known estrogen-induced gene, in a subset of pancreatic neuroendocrine tumors (PanNETs), raise the possibility of hormonal regulation in these tumors.Immunohistochemical expression of estrogen receptors (ERs) ? and ? as well as messenger RNA expression of estrogen-induced genes (PR, EIG121, IGF-1, IGF-1R, sFRP1, and sFRP4) by quantitative reverse transcription-polymerase chain reaction were examined in 131 World Health Organization grade G1 and G2 PanNETs and correlated their expression with clinicopathological features.Thirty-nine PanNETs (30%) showed high positive ER? staining, and 87 cases (66%) had low positive ER? staining; only 5 cases (4%) had no nuclear staining. Pancreatic neuroendocrine tumors with small size (P = 0.02), low World Health Organization grade (P = 0.02), and low American Joint Committee on Cancer stage (P = 0.006) more frequently showed high positive ER? staining. Among the estrogen-induced genes studied, PanNETs had significantly higher expression of PR, EIG121, IGF-1, sFRP1, and sFRP4 compared with normal pancreas, independent of age or sex. High positive ER? staining was associated with an increased expression of PR (P < 0.001) and EIG121 (P = 0.02).Our study showed that PanNETs with favorable prognostic features have higher ER? expression, which is associated with up-regulated PR and EIG121 messenger RNA expression. Estrogen regulation in PanNETs could potentially help in risk stratification and provide a rational target for novel treatment strategies.

SUBMITTER: Estrella JS 

PROVIDER: S-EPMC4628823 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature