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Pancreas. 2014 Oct;43(7):996-1002. doi: 10.1097/MPA.0000000000000203.

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

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1
From the Departments of *Pathology, †Biostatistics, and ‡Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.

Abstract

OBJECTIVE:

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.

METHODS:

Immunohistochemical expression of estrogen receptors (ERs) α and β 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.

RESULTS:

Thirty-nine PanNETs (30%) showed high positive ERβ staining, and 87 cases (66%) had low positive ERβ 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 ERβ 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 ERβ staining was associated with an increased expression of PR (P < 0.001) and EIG121 (P = 0.02).

CONCLUSIONS:

Our study showed that PanNETs with favorable prognostic features have higher ERβ 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.

PMID:
25058880
PMCID:
PMC4628823
DOI:
10.1097/MPA.0000000000000203
[Indexed for MEDLINE]
Free PMC Article

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