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Recently, there is evidence that the number of mast cells in various solid cancers increases with tumor progression. The role of mast cells in promoting tumor progression, however, has not been well studied in pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to investigate the prognostic value of mast cell counts in different zones of the neoplasm in patients with PDAC after curative resection.Numbers of mast cells and microvessels were assessed by immunohistochemistry in tissues from 103 patients with PDAC and 10 patients with normal pancreas. All patients with PDAC underwent partial pancreatic resection. The investigators paid particular attention to the distribution of mast cells in each specimen.High mast cell counts in the intratumoral border zone correlated with the presence of lymphatic and microvascular invasion, lymph node metastasis, and TNM stage, and were an independent prognostic factor for overall survival (P < .001). In contrast, neither in the intratumoral center zone nor in the peritumoral zones was mast cell count associated with OS. Mast cell counts in the intratumoral border zone, but not in the peritumoral or in the intratumoral center zone, were correlated with microvessel counts.The present study shows a zone-specific distribution of mast cells in PDAC and highlights the importance of invasive front in the prognosis of patients with PDAC after curative resection. Zone-specific evaluation of mast cell and microvessel counts may be helpful for prognostic assessment and therapeutic decision making in PDAC.