title: Prognostic Implication of M2 Macrophages Are Determined by the Proportional Balance of Tumor Associated Macrophages and Tumor Infiltrating Lymphocytes in Microsatellite-Unstable Gastric Carcinoma.
abstract: Tumor associated macrophages are major inflammatory cells that play an important role in the tumor microenvironment. In this study, we investigated the prognostic significance of tumor associated macrophages (TAMs) in MSI-high gastric cancers using immunohistochemistry. CD68 and CD163 were used as markers for total infiltrating macrophages and M2-polarized macrophages, respectively. The density of CD68+ or CD163+ TAMs in four different areas (epithelial and stromal compartments of both the tumor center and invasive front) were analyzed in 143 cases of MSI-high advanced gastric cancers using a computerized image analysis system. Gastric cancers were scored as "0" or "1" in each area when the density of CD68+ and CD163+ TAMs was below or above the median value. Low density of CD68+ or CD163+ macrophages in four combined areas was closely associated with more frequent low-grade histology and the intestinal type tumor of the Lauren classification. In survival analysis, the low density of CD163+ TAMs was significantly associated with poor disease-free survival. In multivariate survival analysis, CD163+ TAMs in four combined areas, stromal and epithelial compartments of both tumor center and invasive front were independent prognostic indicator in MSI-high gastric cancers. In addition, the density of CD163+ TAMs correlated with tumor infiltrating lymphocytes (TILs). Our results indicate that the high density of CD163+ TAMs is an independent prognostic marker heralding prolonged disease-free survival and that the prognostic implication of CD163+ TAMs might be determined by the proportional balance of TAMs and TILs in MSI-high gastric cancers.
authors.affiliation: Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.|Department of Pathology, Soonchunhyang University Cheonan Hospital, Cheonan, Korea.
authors.forename: Kyung-Ju
authors.initials: KJ
authors.lastname: Kim
authors.affiliation: Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Xian-Yu
authors.initials: XY
authors.lastname: Wen
authors.affiliation: Department of General Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Han Kwang
authors.initials: HK
authors.lastname: Yang
authors.affiliation: Department of Pathology, and Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Woo Ho
authors.initials: WH
authors.lastname: Kim
authors.affiliation: Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.|Department of Pathology, and Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Gyeong Hoon
authors.initials: GH
authors.lastname: Kang
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D016246:Lymphocytes, Tumor-Infiltrating / Q000502:physiology*; D008264:Macrophages / Q000502:physiology*; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D011956:Receptors, Cell Surface / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000401:mortality; D000098902:CD163 Antigen; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D011956:Receptors, Cell Surface; D000098902:CD163 Antigen; C067980:CD68 antigen, human; D000097382:CD68 Molecule