title: Keratin pearl degradation in oral squamous cell carcinoma: reciprocal roles of neutrophils and macrophages.
abstract: BACKGROUND
  We have reported that neutrophilic infiltration was associated with round-shaped dyskeratosis foci, a kind of keratin pearl, of oral carcinoma in situ and that those inflammatory cells are recruited from intra-epithelially entrapped blood vessels. Based on these lines of evidence, we have formulated a hypothesis that keratin pearls are terminally degraded by neutrophils. To confirm this hypothesis, we investigated immunohistochemically stepwise degradation of keratin pearls in oral squamous cell carcinoma (SCC) to clarify any other type scavenger cells in addition to neutrophils are involved in this particular degradation process.
  
  
  METHODS
  Neutrophils (neutrophil elastase) and macrophage subpopulations (CD68, CD163 and CD204) were immunohistochemically localized in 30 cases of oral SCC with typical round-shaped keratin pearls. SCC cells were revealed by immunohistochemistry for keratin (K) 17, and blood vessels were demonstrated by CD31.
  
  
  RESULTS
  Keratin pearl degradation process was divided into four steps: (i) intact stage: no macrophage infiltration but minimal neutrophils were found in keratin pearls; (ii) neutrophil recruit stage: no macrophage infiltration but focal neutrophilic infiltration within the pearls; (iii) neutrophil predominant stage: dense neutrophil infiltration with minimal macrophages and segregated keratinized cancer cells strongly positive for K17; and (iv) macrophage predominant stage: dense infiltration of CD68-, CD163 (mononuclear)- and CD204 (multinucleated)-positive macrophages engulfing detached keratinized SCC cells.
  
  
  CONCLUSIONS
  Keratin pearl degradation in oral SCC is strictly regulated by two types of scavenger cells: neutrophils, which perform initial tasks, and macrophages, which reciprocally take over from neutrophils the role to finalize the degradation processes.
authors.affiliation: Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Department of Oral Pathology, Faculty of Dentistry, Tanta University, Tanta, Egypt.
authors.forename: Ahmed A M
authors.initials: AA
authors.lastname: Essa
authors.forename: Manabu
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Maruyama
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Abé
authors.forename: Hamzah
authors.initials: H
authors.lastname: Babkair
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
authors.forename: Takashi
authors.initials: T
authors.lastname: Saku
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D053537:Keratin-17 / Q000032:analysis; D007633:Keratins / Q000378:metabolism*; D019272:Leukocyte Elastase / Q000032:analysis; D008262:Macrophage Activation / Q000502:physiology; D008264:Macrophages / Q000145:classification / Q000378:metabolism*; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D020556:Neutrophil Infiltration / Q000502:physiology; D009504:Neutrophils / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D059748:Proteolysis; D011956:Receptors, Cell Surface / Q000032:analysis; D051116:Receptors, Scavenger / Q000032:analysis; D051117:Scavenger Receptors, Class A / Q000032:analysis; D000098902:CD163 Antigen; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D053537:Keratin-17; D007633:Keratins; D019272:Leukocyte Elastase; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011956:Receptors, Cell Surface; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D000098902:CD163 Antigen; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C495139:MSR1 protein, human
keywords: keratin 17; keratin pearl degradation; macrophages; neutrophils; oral squamous cell carcinoma