title: Unique intravascular tumor microenvironment predicting recurrence of lung squamous cell carcinoma.
abstract: OBJECTIVE
  Histological vascular invasion (VI) by tumors is a risk factor for recurrence after surgical resection. However, VI features vary histologically. The aim of this study was to identify characteristic VI features that are associated with recurrence in squamous cell carcinoma (SCC) of the lung.
  
  
  METHODS
  We enrolled 149 patients with pathological stage I primary lung SCC in this study and examined whether the presence, frequency, and size of VI were associated with recurrence. We also evaluated immunophenotypes of carcinoma cells and stromal cells within VI areas.
  
  
  RESULTS
  Of the 149 patients, 58 had tumors with VI. The presence of VI was significantly correlated with shorter recurrence-free survival (RFS) (P = 0.018). Although VI frequency was not associated with RFS, larger VI size (>425 µm) was significantly correlated with shorter RFS (P = 0.003). Carcinoma cells within larger VI areas expressed significantly higher levels of podoplanin, cancer stem cell marker (P = 0.039); higher numbers of CD34(+) microvessels (P = 0.009), CD204(+) macrophages (P = 0.026), and α-SMA(+) myofibroblasts (P = 0.056) were present within larger VI areas than within smaller VI ones.
  
  
  CONCLUSIONS
  Our results indicate that larger VI areas are a predictor for recurrence in lung SCC; also, within the larger blood vessel, cancer stem cells and abundant stromal cells can create a more favorable microenvironment for tumor metastasis.
authors.affiliation: Division of Pathology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, 277-8577, Japan.|Department of Thoracic Oncology, National Cancer Center, Kashiwa, Chiba, Japan.|Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Sendagi, Bunkyo City, Tokyo, Japan.
authors.forename: Kakeru
authors.initials: K
authors.lastname: Hisakane
authors.affiliation: Division of Pathology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, 277-8577, Japan.|Department of Thoracic Oncology, National Cancer Center, Kashiwa, Chiba, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Saruwatari
authors.affiliation: Division of Pathology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, 277-8577, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fujii
authors.affiliation: Department of Thoracic Oncology, National Cancer Center, Kashiwa, Chiba, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kirita
authors.affiliation: Department of Thoracic Oncology, National Cancer Center, Kashiwa, Chiba, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Umemura
authors.affiliation: Department of Thoracic Oncology, National Cancer Center, Kashiwa, Chiba, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Matsumoto
authors.affiliation: Department of Thoracic Oncology, National Cancer Center, Kashiwa, Chiba, Japan.
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Yoh
authors.affiliation: Department of Thoracic Oncology, National Cancer Center, Kashiwa, Chiba, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Niho
authors.affiliation: Department of Thoracic Oncology, National Cancer Center, Kashiwa, Chiba, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Ohmatsu
authors.affiliation: Division of Pathology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, 277-8577, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kuwata
authors.affiliation: Division of Pathology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, 277-8577, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ochiai
authors.affiliation: Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Sendagi, Bunkyo City, Tokyo, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Gemma
authors.affiliation: Department of Thoracic Surgery, National Cancer Center, Kashiwa, Chiba, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tsuboi
authors.affiliation: Department of Thoracic Oncology, National Cancer Center, Kashiwa, Chiba, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Goto
authors.affiliation: Division of Pathology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, 277-8577, Japan. gishii@east.ncc.go.jp.
authors.forename: Genichiro
authors.initials: G
authors.lastname: Ishii
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001808:Blood Vessels / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000098:blood supply / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D016019:Survival Analysis; D059016:Tumor Microenvironment / Q000502:physiology*
keywords: Intravascular tumor microenvironment; Lung squamous cell carcinoma; Pathology; Vascular invasion