Macrophage subtype predicts lymph node metastasis in oesophageal adenocarcinoma and promotes cancer cell invasion in vitro.
BACKGROUND
Currently, there is a lack of ideal biomarkers for predicting nodal status in preoperative stage of oesophageal adenocarcinoma (EAC) to aid optimising therapeutic options. We studied the potential of applying subtype macrophages to predict lymph node metastasis and prognosis in EAC.


METHODS
Fifty-three EAC resection specimens were immunostained with CD68, CD40 (M1), and CD163 (M2). Lymphatic vessel density (LVD) was estimated with the staining of D2-40. Subsequently, we tested if M2d macrophage could promote EAC cell migration and invasion.


RESULTS
In EAC without neoadjuvant treatment, an increase in M2-like macrophage was associated with poor patient survival, independent of the locations of macrophages in tumour. The M2/M1 ratio that represented the balance between M2- and M1-like macrophages was significantly higher in nodal-positive EACs than that in nodal-negative EACs, and inversely correlated with patient overall survival. The M2/M1 ratio was not related to LVD. EAC cell polarised THP1 cell into M2d-like macrophage, which promoted EAC cell migration and invasion. Neoadjuvant therapy appeared to diminish the correlation between the M2/M1 ratio and survival.


CONCLUSIONS
The ratio of M2/M1 macrophage may serve as a sensitive marker to predict lymph node metastasis and poor prognosis in EAC without neoadjuvant therapy. M2d macrophage may have important roles in EAC metastasis.
Department of Pathology, NYU School of Medicine, 560 First Avenue, New York, NY, USA.
Wenqing
W
Cao
Department of Surgery, University of Rochester Medical Center, Rochester, NY, USA.
Jeffrey H
JH
Peters
Department of Surgery, University of Rochester Medical Center, Rochester, NY, USA.
Dylan
D
Nieman
Department of Pathology and Laboratory Medicine, University of Rochester Medical Centre, 601 Elmwood Avenue, Box 626, Rochester, NY, USA.
Meenal
M
Sharma
Department of Surgery, University of Rochester Medical Center, Rochester, NY, USA.
Thomas
T
Watson
Department of Pathology and Laboratory Medicine, University of Rochester Medical Centre, 601 Elmwood Avenue, Box 626, Rochester, NY, USA.
JiangZhou
J
Yu
D000230:Adenocarcinoma / Q000276:immunology / Q000401:mortality / Q000556:secondary*; D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D002465:Cell Movement; D004938:Esophageal Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000473:pathology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D055815:Young Adult