title: Cancer-associated fibroblasts and CD163-positive macrophages in oral squamous cell carcinoma: their clinicopathological and prognostic significance.
abstract: BACKGROUND
  Stromal cells are believed to affect cancer invasion and metastasis. The purpose of this study was to evaluate the distribution of cancer-associated fibroblasts (CAFs) and the incidence of tumor-associated macrophages (TAMs) in oral squamous cell carcinoma (OSCC), focusing on clinicopathological factors and patient prognosis, as well as cancer invasion.
  
  
  METHODS
  The study included 108 patients with OSCC. Anti-α-smooth muscle actin, CD68, and CD163 antibodies were used to identify CAFs and TAMs. CAFs were divided into 4 grades on the basis of staining intensity: negative (0), scanty (1), focal (2), and abundant (3). The most intensive areas of macrophage concentration in each tumor invasive stroma were also evaluated.
  
  
  RESULTS
  The cancer specimens were divided into Grade 0/1, Grade 2, and Grade 3 on the basis of CAF grade. In addition, they were divided into low- and high-grade groups on the basis of the number of CD68-positive and CD163-positive macrophages. The latter were significantly increased in the Grade 2 CAF group compared to the Grade 0/1 group (P = 0.009). Kaplan-Meier and multivariate survival analyses revealed that Grade 2 CAFs (P = 0.003) and high CD163-positive macrophage levels (P = 0.007) significantly correlated with a poor outcome in patients with OSCC, and that a high CD163-positive macrophage level was a significant and an independent prognostic factor (P = 0.045).
  
  
  CONCLUSIONS
  Cancer-associated fibroblasts and CD163-positive macrophages may be potential prognostic predictors of OSCC.
authors.affiliation: Division of Organ Pathology, Department of Microbiology and Pathology, Faculty of Medicine, Tottori University, Tottori, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Fujii
authors.forename: Kohei
authors.initials: K
authors.lastname: Shomori
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Shiomi
authors.forename: Motoki
authors.initials: M
authors.lastname: Nakabayashi
authors.forename: Chikako
authors.initials: C
authors.lastname: Takeda
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ryoke
authors.forename: Hisao
authors.initials: H
authors.lastname: Ito
mesh_terms: D000199:Actins / Q000032:analysis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis*; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000601:surgery; D002467:Cell Nucleus / Q000648:ultrastructure; D004848:Epithelium / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000473:pathology*; D005887:Gingival Neoplasms / Q000473:pathology; D006801:Humans; D008264:Macrophages / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000473:pathology; D009062:Mouth Neoplasms / Q000473:pathology* / Q000601:surgery; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000032:analysis*; D051116:Receptors, Scavenger / Q000032:analysis*; D017154:Stromal Cells / Q000473:pathology; D015996:Survival Rate; D014062:Tongue Neoplasms / Q000473:pathology; D055815:Young Adult; D000098902:CD163 Antigen; D000097382:CD68 Molecule
chemical_list: D000199:Actins; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D011956:Receptors, Cell Surface; D051116:Receptors, Scavenger; D000098902:CD163 Antigen; C541116:ACTA2 protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule