Estrogen-Induced Genes Are Expressed in Pancreatic Neuroendocrine Tumors
Ly T Ma, Huamin Wang, Asif Rashid, Russell R Broaddus, Jeannelyn S Estrella. U.T. M.D. Anderson Cancer Center, Houston, TX
Background: High progesterone receptor (PR) expression, a well-known estrogen-induced gene (EIG), confers better prognosis in pancreatic neuroendocrine tumors (PanNETs). We, therefore, assessed mRNA expression of other EIGs and their prognostic significance in PanNETs. We also examined ERβ expression in a subset of PanNETs; we hypothesize that transcription of EIGs may be driven by ERβ, as ERα is not expressed in these tumors.
Design: 138 primary resected WHO G1-G2 PanNETs were analyzed for EIG [PR, insulin-like growth factor (IGF)-1, IGF-1R, EIG121, secreted frizzled-related protein (sFRP)-1 and sFRP-4] mRNA expression by RT-PCR and correlated with clinicopathologic parameters. Adjacent normal pancreas (42 cases) served as control. A subset of tumors (40 cases) were evaluated for ERβ immunohistochemical expression and correlated with EIG mRNA. Allred scoring was used to categorize ERβ staining as follows: diffuse=7-8/8; weak=3-6/8; negative=0-2/8.
Results: Results are summarized in Table 1. PanNETs had significantly higher EIG mRNA levels compared to normal pancreas, regardless of gender. Diffuse ERβ positivity was seen in 24 of 40 (60%), while the remaining 40% showed weak positivity; none had negative staining. EIG121 mRNA was 10-fold higher compared to other EIGs and high mRNA expression correlated with diffuse ERβ positivity. High IGF-1R mRNA expression correlated wtih low WHO grade and AJCC stage and also showed diffuse ERβ positivity.
|Estrogen-induced gene (mean mRNA/mean 18SrRNA) x10^4|
|Tumor vs. Normal (p value)||<0.001||NS||0.04||<0.001||0.003||0.02|
|Gender (p value)||NS||NS||NS||NS||NS||NS|
|WHO Grade (p value)||NS||NS||0.008||NS||0.003||NS|
|G1 (low, n=69)||71||2.3||43||440||7.3||57|
|G2 (intermediate, n=60)||55||2.4||25||480||21||73|
|Stage (p value)||0.05||NS||0.01||NS||NS||NS|
|Estrogen Receptor β||0.008||NS||0.03||0.007||NS||0.02|