Background: The erythropoietin-producing hepatocellular (EPH) receptor tyrosine kinases (RTKs) are involved in human carcinogenesis. EphA2, one member of the EPH family, is associated with tumorigenesis and tumor neovascularization in a variety of human cancers. Pancreatic adenocarcinoma cells differentially express EphA2. More recent data suggest that EphA2 siRNA suppresses EphA2 expression, cellular invasiveness, and FAK phosphorylation in vitro and retards tumor growth and inhibits metastasis in a mouse model in vivo. In contrast, EphA2 expression in human primary pancreatic adenocarcinoma has never been reported to date, we investigated the expression of EphA2 in human pancreatic adenocarcinoma and normal pancreatic duct by immunohistochemistry,. Materials and Methods: We performed immunohistochemical analysis of 32 surgical resected pancreatic adenocarcinoma specimens in our institute between 1987 and 2004. Immunohistochemical staining was performed with EphA2 antibody (Santa Cruz, rabbit polyclonal). Two pathologists graded the percentage of stained cells from 0 to 2+ [0 (less than 10% of the cells), 1+ (10-50% of the cells), 2+ (>50% of the cells)]. More than 10% of tumor cells staining were defined as positive. Clinical and pathological data and EphA2 expression were examined compared. Results: Twenty-one (65.6%) of the 32 pancreatic adenocarcinoma tissues stained positive, 3 showed 1+ staining and 18 showed 2+ staining. On the other hand, three (11.1%) of the 27 normal pancreatic duct tissues stained positive, 24 showed 0 staining and 3 showed 2+ staining. EphA2 was significantly highly expressed in tumor tissue than in normal tissue (p<0.001). EphA2 was more highly expressed in advanced clinical stages, in 3 (42.9%) of the 7 cases of stage I and II, and 18 (72.0%) of the 25 cases of stage III and IV, respectively. Histologically, EphA2 was more highly expressed in well differentiated type than in poorly differentiated type [7 (87.5%) of the 8 cases of well differentiated type, 11 (68.8%) of the 16 of moderately differentiated type, and 3 (42.9%) of the 7 cases of poorly differentiated type]. Recurrence rate, survival time was not associated with EphA2 expression. Conclusions: Our preliminary data suggest that EphA2 may provide a molecular marker to identify progressed pancreatic adenocarcinoma. The high levels of EphA2 in pancreatic adenocarcinoma may provide an opportunity of using EphA2 as a therapeutic targeting.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]