title: Angiogenesis in superficial esophageal squamous cell carcinoma: assessment of microvessel density based on immunostaining for CD34 and CD105.
abstract: OBJECTIVE
  The esophagus is the only organ where changes in the superficial microvasculature from normal squamous epithelium to invasive cancer are evident by magnifying endoscopy. We investigated in detail the features of angiogenesis in early-stage esophageal cancer using CD34 and CD105 immunostaining, and also the correlation between angiogenesis and mononuclear cell infiltration.
  
  
  METHODS
  Using 10 samples of normal squamous epithelium, 7 samples of low-grade intraepithelial neoplasia, and 45 samples of superficial esophageal cancer, we determined the microvessel density at hot spots showing positive staining for CD34 and CD105. We observed the histological features of CD34- and CD105-positive microvessels that corresponded to observations made by magnifying endoscopy. We then investigated the correlation between microvessel density and each histological situation or the grade of mononuclear cell infiltration.
  
  
  RESULTS
  The histological features of CD34- and CD105-positive microvessels were able to explain the morphological changes in the microvasculature during cancer progression observed by magnifying endoscopy. The microvessel density for CD34 or CD105 was significantly correlated with each of the histological types (P < 0.001, rS = 0.51 and 0.76, respectively). Mononuclear cell infiltration at CD105 hot spots was most frequent in M1 and M2 cancer (94.7%). The correlation between the degree of mononuclear cell infiltration and microvessel density for CD105 staining was also significant (P < 0.001, rS = 0.49).
  
  
  CONCLUSIONS
  The microvessel density based on CD34 and CD105 immunostaining can be used to corroborate observations of superficial esophageal squamous cell carcinoma made by magnifying endoscopy. Mononuclear cell infiltration may play an important role in angiogenesis at the early stage of cancer progression.
authors.affiliation: Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Saitama kuma7srg1@gmail.com.
authors.forename: Youichi
authors.initials: Y
authors.lastname: Kumagai
authors.affiliation: Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Saitama.
authors.forename: Jun
authors.initials: J
authors.lastname: Sobajima
authors.affiliation: Department of Pathology, Saitama Medical Center, Saitama Medical University, Saitama.
authors.forename: Morihiro
authors.initials: M
authors.lastname: Higashi
authors.affiliation: Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Saitama.
authors.forename: Toru
authors.initials: T
authors.lastname: Ishiguro
authors.affiliation: Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Saitama.
authors.forename: Minoru
authors.initials: M
authors.lastname: Fukuchi
authors.affiliation: Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Saitama.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Ishibashi
authors.affiliation: Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Saitama.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Baba
authors.affiliation: Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Saitama.
authors.forename: Erito
authors.initials: E
authors.lastname: Mochiki
authors.affiliation: Department of Gastroenterology and Hepatology, Saitama Medical Center, Saitama Medical University, Saitama.
authors.forename: Koji
authors.initials: K
authors.lastname: Yakabi
authors.affiliation: Department of Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Tatsuyuki
authors.initials: T
authors.lastname: Kawano
authors.affiliation: Department of Pathology, Saitama Medical Center, Saitama Medical University, Saitama.
authors.forename: Junichi
authors.initials: J
authors.lastname: Tamaru
authors.affiliation: Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Saitama.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Ishida
mesh_terms: D015703:Antigens, CD / Q000032:analysis*; D018952:Antigens, CD34 / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000098:blood supply* / Q000473:pathology; D018450:Disease Progression; D000071063:Endoglin; D004938:Esophageal Neoplasms / Q000098:blood supply* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D004945:Esophagoscopy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007963:Leukocytes, Mononuclear; D008297:Male; D055806:Microvessels / Q000473:pathology*; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000473:pathology*; D011956:Receptors, Cell Surface / Q000032:analysis*
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface
keywords: CD105; CD34; angiogenesis; esophageal cancer; microvessel density