[1781] 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.

Correlation between Clinicopathologic Parameters and Estrogen-induced Genes in Pancreatic Neuroendocrine Tumors
 Estrogen-induced gene (mean mRNA/mean 18SrRNA) x10^4 
 PRIGF-1IGF-1REIG121sFRP-1sFRP-4
Tumor vs. Normal (p value)<0.001NS0.04<0.0010.0030.02
Normal (n=42)41.7221102.021
Tumor (n=138)632.3354701562
Gender (p value)NSNSNSNSNSNS
Female (n=53)572.3365301263
Male (n=85)662.4334301761
WHO Grade (p value)NSNS0.008NS0.003NS
G1 (low, n=69)712.3434407.357
G2 (intermediate, n=60)552.4254802173
Stage (p value)0.05NS0.01NSNSNS
1-2A (n=63)711.9415001456
2B (n=34)812.5415101479
4 (n=41)352.9194001757
Estrogen Receptor β0.008NS0.030.007NS0.02
Diffuse (n=24)1151.6646301327
Weak (n=16)183.4223001577
PR-progesterone receptor; IGF-insulin-like growth factor; EIG121-estrogen-induced gene 121; sFRP-secreted frizzled-related protein.


Conclusions: In a subset of PanNETs, high ERβ immunohistochemical expression correlated with high mRNA expression of EIGs predicting low grade and stage, suggesting a protective role in PanNETs. ERβ activation may serve as a new hormonal therapy for some patients with PanNETs.
Category: Pancreas

Tuesday, March 5, 2013 9:30 AM

Poster Session III # 208, Tuesday Morning

 

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