Prognostic impact of M2 macrophages at neural invasion in patients with invasive ductal carcinoma of the pancreas.
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.
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.
Motokazu
M
Sugimoto
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.
Shuichi
S
Mitsunaga
Division of Pathology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Japan.
Kiyoshi
K
Yoshikawa
Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Japan.
Yuichiro
Y
Kato
Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Japan.
Naoto
N
Gotohda
Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Japan.
Shinichiro
S
Takahashi
Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Japan.
Masaru
M
Konishi
Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Japan.
Masafumi
M
Ikeda
Division of Pathology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Japan.
Motohiro
M
Kojima
Division of Pathology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Japan. Electronic address: aochiai@east.ncc.go.jp.
Atsushi
A
Ochiai
Department of Surgery, Toho University School of Medicine, Japan.
Hironori
H
Kaneko
D000368:Aged; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D017615:Enteric Nervous System / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000473:pathology*; D008297:Male; D051379:Mice; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery; D011379:Prognosis; D051117:Scavenger Receptors, Class A / Q000378:metabolism; D016019:Survival Analysis
C495139:MSR1 protein, human; D051117:Scavenger Receptors, Class A
Adjuvant chemotherapy; Locoregional recurrence; M2 macrophages; Neural invasion; Overall survival; Pancreatic cancer; Pancreaticoduodenectomy; Peritoneal dissemination