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Increased epithelial and serum expression of macrophage migration inhibitory factor (MIF) in gastric cancer: potential role of MIF in gastric carcinogenesis
  1. X-X He1,
  2. J Yang2,
  3. Y-W Ding1,
  4. W Liu1,
  5. Q-Y Shen1,
  6. H H-X Xia3
  1. 1Department of Gastroenterology, The Second Affiliated Hospital of Guangzhou Medical College, Guangzhou, Guangdong, China
  2. 2Department of Epidemiology, Roswell Park Cancer Institute, Buffalo, New York, USA
  3. 3Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
  1. Correspondence to:
    Dr H H-X Xia
    Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China; hhxxia{at}


Aims: Macrophage migration inhibitory factor (MIF) is implicated in tumorigenesis. This study was conducted to determine whether MIF expression is associated with gastric pathology and whether MIF expression is increased in malignant gastric cells in vitro.

Materials and methods: Patients with a normal gastric mucosa, Helicobacter pylori infected gastritis, intestinal metaplasia, and gastric adenocarcinoma were included. Immunohistochemistry and enzyme linked immunosorbent assay (ELISA) were used to determine MIF expression in gastric epithelial cells and MIF levels in serum, respectively. Five gastric cancer cell lines (AGS, MKN-45, MKN-28, MGC-803, and SGC-7901) and one non-malignant gastric cell line (GES-1) were cultured for 24 hours. MIF protein in the supernatant and MIF mRNA in cultured cells were measured by ELISA and reverse transcription-polymerase chain reaction, respectively.

Results: The percentage of MIF expressing epithelial cells was low in normal mucosa (12%) but substantially higher in gastritis (52%), intestinal metaplasia (66%), and gastric cancer (96%) (p<0.001, ANOVA). Serum MIF levels were low in patients with a normal mucosa (576 (82) pg/ml) but higher in patients with gastritis (2100 (349) pg/ml), intestinal metaplasia (4498 (253) pg/ml), and gastric cancer (9737 (1249) pg/ml) (p<0.001, ANOVA). There was a correlation between epithelial MIF expression and serum MIF levels (r = 0.776, p<0.001). In vitro, expression of MIF protein and mRNA was increased in malignant cells compared with non-malignant cells.

Conclusions: Epithelial and serum MIF expression was progressively increased in H pylori induced gastritis, intestinal metaplasia, and gastric cancer, suggesting that MIF is involved in gastric carcinogenesis and may be a valuable biomarker for the early detection of gastric cancer.

  • MIF, macrophage migration inhibitory factor
  • ELISA, enzyme linked immunosorbent assay
  • RT-PCR, reverse transcription-polymerase chain reaction
  • LI, labelling index
  • macrophage migration inhibitory factor
  • Helicobacter pylori infection
  • intestinal metaplasia
  • gastric cancer

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  • Published online first 17 February 2006

  • Conflict of interest: None declared.