[27] Expression of Yes-Associated Protein Increases in Pancreatic Tumors with High Tumor Burden, a Study Utilizing Rapid Autopsy Technique

DM Lam-Himlin, C Iacobuzio-Donahue, RA Anders. Johns Hopkins Hospital, Baltimore, MD

Background: The Hippo signaling pathway is a highly conserved potent regulator of mammalian cell growth, division, and apoptosis. Yes-associated protein (YAP) is the nuclear effector of the Hippo pathway. We and others have reported that, in humans, there is amplification of the chromosome region containing the YAP gene (11q22), and that over-expression exists in several human tumor types. Utilizing a unique resource involving rapid autopsy technique, we investigated YAP expression in pancreatic cancers from patients with varying tumor burdens.
Design: Tissue microarrays containing pancreatic tumors (n= 140), harvested via rapid autopsies from 36 patients, were stained with YAP by immunohistochemistry. Autopsy cases were stratified by extent of tumor burden as follows: Primary Only (metastatic burden=0), Low (1-10 metatastases), Extensive (11-99), and Widespread (100-1000's). The YAP expression intensity and distribution were evaluated in these tissues with non-neoplastic pancreatic epithelium as controls (n=10). For each patient, the nuclear and cytoplasmic YAP expression intensity was scored on a four-point scale in multiple samples and averaged to yield a positive or negative result.
Results: Control tissues of non-neoplastic pancreatic epithelium showed 80% nuclear (Nuc) reactivity with YAP and 30% cytoplasmic (Cyt). Pancreatic tumors with primary only showed 83% Nuc and 17% Cyt; low burden showed 71% Nuc and 43% Cyt; extensive burden showed 86% Nuc and 43% Cyt; widespread burden showed 100% Nuc and 56% Cyt.

YAP Staining in Pancreatic Ductal Adenocarcinomas

Tissue	Nuclear Staining	Cytoplasmic Staining
Non-neoplastic Ductal Epithelium (Control)	80% (8/10)	30% (3/10)
Primary Only (Metastatic Burden = 0)	83% (5/6)	17% (1/6)
Low Metastatic Burden (≤10)	71% (5/7)	43% (3/7)
Extensive Metastatic Burden (10-99)	86% (6/7)	43% (3/7)
Widespread Metastatic Burden (100-1000's)	100% (16/16)	56% (9/16)

Conclusions: Pancreatic carcinomas demonstrating widespread tumor burden show increased nuclear expression of YAP compared to non-neoplastic tissues (p< 0.7) and low metastatic burden tumors (p<0.8). Our findings are limited by the number of rapid autopsies available for analysis. However, our findings suggest that activation of the Hippo signaling pathway may occur through YAP as part of normal pancreatic epithelial homeostasis and has increased expression in tumors with widespread metastatic behavior.
Category: Autopsy

Wednesday, March 24, 2010 9:30 AM

Poster Session V # 15, Wednesday Morning