[1527] Hedgehog Signaling Pathway Is Frequently Activated in Pancreatic Neuroendocrine Tumors.

Wendy L Frankel, Mark Bloomston, Xiaoping Zhou. The Ohio State University, Columbus

Background: The Hedgehog (Hh) signaling pathway plays a critical role in embryo development and governs a diverse array of cellular processes including cell proliferation, differentiation, and tissue patterning. Aberrant activation of this pathway, either by ligand expression, activating mutation/amplification or by loss of function of the core components, has been described in a number of human cancers. Small molecule (s) of Hh inhibitor is available and has shown promising in vivo and in vitro anti-tumor activity. We assessed Hh signaling activity in a cohort of pancreatic neuroendocrine tumors (NET) using immunohistochemistry for SHH and PTCH1.
Design: Tissue microarrays were constructed from formalin-fixed, paraffin-embedded blocks of 98 primary pancreatic NET and 7 normal pancreata (controls) from departmental archives and stained with SHH, PTCH1 and Ki-67. Expression intensity for SHH and PTCH1 was scored as 0 (absent), 1+ (weak), and 2+ (modest to high). The proliferation index was assessed using the percentage of tumor cells positive for Ki-67 nuclear labelling and grouped into ≤2%, 3-20%, >20%.
Results: All 7 normal islets expressed weak levels (1+) of SHH and PTCH1. Modest to high levels (2+) of SHH and PTCH1 expression were detected in 48 (49%) and 11 (11%) NET, respectively. No expression of SHH and PTCH1 was seen in 2 (2%) and 15 (16%) tumors, respectively. Seventy-two tumors showed a proliferation index of ≤2%, 24 of 3-20%, and 4 of >20%. No association was observed between SHH or PTCH1 expression and the proliferation index in NET.

Expression of SHH and PTCH1 in pancreatic NET
Staining IntensitySHH (n = 98)PTCH1 (n = 97)
2+48 (49%)11 (11%)
1+48 (49%)71 (73%)
02 (2%)15 (16%)

Conclusions: Aberrant activation of the Hh pathway was present in up to half of pancreatic NET. Our findings suggest that Hh signaling pathway may represent a rational therapeutic target in pancreatic NET.
Category: Liver & Pancreas

Tuesday, March 1, 2011 1:00 PM

Poster Session IV # 217, Tuesday Afternoon


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