Stromal osteonectin overexpression is associated with poor outcome in patients with ampullary cancer

Background: Osteonectin has been suggested to be important in the progression of pancreatic cancer but has not been correlated with survival. We determined the osteonectin expression and its influence on survival in patients with ampullary carcinoma. Methods: Tissue microarrays were constructed from the tumors of 56 patients with ampullary cancer undergoing pancreaticoduodenectomy. Immunohistochemical staining for osteonectin was undertaken and compared with staining in chronic pancreatitis (n = 13) and normal pancreas (n = 19). Survival curves were created by the Kaplan-Meier method and compared by log rank analysis. Median follow-up for all living patients with ampullary cancer was 69.6 months. Results: Osteonectin was significantly (P < .05, Fisher's exact test) overexpressed in the stroma of ampullary cancers (90%) relative to chronic pancreatitis (62%) and normal pancreas (0%). Tumors expressing osteonectin were more likely to have nodal metastases than those lacking osteonectin expression (48% vs. 0%, P = .06, Fisher's exact test) and showed decreased survival. Node-negative status, pylorus preservation at the time of pancreaticoduodenectomy, and lack of osteonectin expression were predictors of prolonged survival by multivariate analysis. Conclusions: Although the importance of tumor-stroma interactions in periampullary cancers is not fully understood, our data suggest that osteonectin is an integral stromal element in ampullary cancers, and its overexpression is associated with decreased survival.