Motokazu Sugimoto1, Shuichi Mitsunaga2, Kiyoshi Yoshikawa3, Yuichiro Kato4, Naoto Gotohda4, Shinichiro Takahashi4, Masaru Konishi4, Masafumi Ikeda5, Motohiro Kojima3, Atsushi Ochiai6, Hironori Kaneko7. 1. Division of Pathology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Japan; Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Japan; Department of Surgery, Toho University School of Medicine, Japan. 2. Division of Pathology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Japan; Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Japan. 3. Division of Pathology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Japan. 4. Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Japan. 5. Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Japan. 6. Division of Pathology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Japan. Electronic address: aochiai@east.ncc.go.jp. 7. Department of Surgery, Toho University School of Medicine, Japan.
Abstract
BACKGROUND: Neural invasion is a characteristic pattern of invasion and an important prognostic factor for invasive ductal carcinoma (IDC) of the pancreas. M2 macrophages have reportedly been associated with poor prognosis in various cancers. The aim of the present study was to investigate the prognostic impact of M2 macrophages at extrapancreatic nerve plexus invasion (plx-inv) of pancreatic IDC. METHODS: Participants comprised 170 patients who underwent curative pancreaticoduodenectomy for pancreatic IDC. Immunohistochemical examination of surgical specimens was performed by using CD204 as an M2 macrophage marker, and the area of immunopositive cells was calculated automatically. Prognostic analyses of clinicopathological factors including CD204-positive cells at plx-inv were performed. RESULTS: Plx-inv was observed in 91 patients (53.5%). Forty-eight patients showed a high percentage of CD204-positive cell area at plx-inv (plx-inv CD204%(high)). Plx-inv CD204%(high) was an independent predictor of poor outcomes for overall survival (OS) (P<0.001) and disease-free survival (DFS) (P<0.001). Patients with plx-inv CD204%(high) showed a shorter time to peritoneal dissemination (P<0.001) and locoregonal recurrence (P<0.001). In patients who underwent adjuvant chemotherapy, plx-inv CD204%(high) was correlated with shorter OS (P=0.011) and DFS (P=0.038) in multivariate analysis. CONCLUSIONS: Plx-inv CD204%(high) was associated with shortened OS and DFS and early recurrence in the peritoneal cavity and locoregional space. The prognostic value of plx-inv CD204%(high) was also applicable to patients who received adjuvant chemotherapy. High accumulation of M2 macrophages at plx-inv represents an important predictor of poor prognosis.
BACKGROUND: Neural invasion is a characteristic pattern of invasion and an important prognostic factor for invasive ductal carcinoma (IDC) of the pancreas. M2 macrophages have reportedly been associated with poor prognosis in various cancers. The aim of the present study was to investigate the prognostic impact of M2 macrophages at extrapancreatic nerve plexus invasion (plx-inv) of pancreatic IDC. METHODS:Participants comprised 170 patients who underwent curative pancreaticoduodenectomy for pancreatic IDC. Immunohistochemical examination of surgical specimens was performed by using CD204 as an M2 macrophage marker, and the area of immunopositive cells was calculated automatically. Prognostic analyses of clinicopathological factors including CD204-positive cells at plx-inv were performed. RESULTS: Plx-inv was observed in 91 patients (53.5%). Forty-eight patients showed a high percentage of CD204-positive cell area at plx-inv (plx-inv CD204%(high)). Plx-inv CD204%(high) was an independent predictor of poor outcomes for overall survival (OS) (P<0.001) and disease-free survival (DFS) (P<0.001). Patients with plx-inv CD204%(high) showed a shorter time to peritoneal dissemination (P<0.001) and locoregonal recurrence (P<0.001). In patients who underwent adjuvant chemotherapy, plx-inv CD204%(high) was correlated with shorter OS (P=0.011) and DFS (P=0.038) in multivariate analysis. CONCLUSIONS: Plx-inv CD204%(high) was associated with shortened OS and DFS and early recurrence in the peritoneal cavity and locoregional space. The prognostic value of plx-inv CD204%(high) was also applicable to patients who received adjuvant chemotherapy. High accumulation of M2 macrophages at plx-inv represents an important predictor of poor prognosis.
Authors: Guido Eibl; Zobeida Cruz-Monserrate; Murray Korc; Maxim S Petrov; Mark O Goodarzi; William E Fisher; Aida Habtezion; Aurelia Lugea; Stephen J Pandol; Phil A Hart; Dana K Andersen Journal: J Acad Nutr Diet Date: 2017-09-12 Impact factor: 4.910