Background: Most pancreatic ductal adenocarcinomas (PDACs) metastasize even after curative resection. Our goal was to investigate the important factors affecting metastasis and overall survival (OS).
Methods: We studied 88 PDACs with R0 resection and evaluated immunohistochemical markers on tissue microarrays to assess the expression levels of the following: EGFR, amphiregulin, VEGF, p-c-met, MMP2, MMP7, MMP9, CXCR3, and CXCR4.
Results: The median OS in patients who had positive versus negative expression of AREG and MMP9 were 25 versus 16 months and 24 versus 13 months, respectively (P = 0.03, P = 0.006). However, the median OS in patients with positive versus negative expression of MMP2 was 22 versus 37 months (P = 0.04). Immunoprofiles also revealed that patients with positive expression of p-c-met or VEGF had significantly shorter distant metastasis-free survival. Adjuvant treatment, postoperative decrease of CA 19-9, angiolymphatic invasion, AREG, and MMP2 were independent prognostic factors affecting OS in multivariate analysis.
Conclusions: Immunoprofiles revealed the groups with unfavorable tumor biology: negative expression of AREG and positive expression of MMP2. Also, high immunoreactivity of p-c-met or VEGF seemed to be associated with early distant organ metastasis in R0 resected PDACs; however, they still need to be further investigated. These results may give us useful insights in understanding the tumor biology and the patterns of PDAC dissemination.