title: The clinical significance of the tumor cell D2-40 immunoreactivity in non-small cell lung cancer.
abstract: BACKGROUND
  A monoclonal antibody D2-40 has been widely used for tumor lymphangiogenesis and lymphatic vessel invasion (LVI) in human cancers. However, the clinical significance of the tumor cell D2-40 immunoreactivity has not been clearly understood.
  
  
  METHODS
  We evaluated the tumor cell D2-40 immunoreactivity in non-small cell lung cancer (NSCLC). One hundred and forty-seven NSCLC patients were investigated. Immunohistochemistry using D2-40 was performed to evaluate the tumor cell D2-40 immunoreactivity, micro-lymphatic vessel density (Micro-LVD) and LVI. The intratumoral microvessels density (MVD) was evaluated by the CD34-immunostaining, and tumor proliferation was evaluated by the Ki-67-immunostaining.
  
  
  RESULTS
  The percentage of D2-40-positive tumor cells was significantly higher in squamous cell carcinomas than in adenocarcinomas (P<0.0001), and all D2-40-strong tumors were squamous cell carcinomas. The percentage of D2-40-strong tumors was significantly higher in moderately to poorly differentiated tumors than in well-differentiated tumors (P=0.0332). Furthermore, the Ki-67 proliferation index in D2-40-strong tumors was significantly the highest. However, the tumor cell D2-40 immunoreactivity was not associated with Micro-LVD, LVI, or MVD. Regarding the patient survival, the overall survival was significantly lower in patients with D2-40-strong tumors than in patients with D2-40-negative or D2-40-weak tumors (P=0.0005). Multivariate analyses also revealed the tumor cell D2-40 immunoreactivity to be a significant prognostic factor of poor prognosis for NSCLC patients (P=0.0007).
  
  
  CONCLUSIONS
  The D2-40 immunostaining is useful to identify aggressive squamous cell carcinomas of the lung.
authors.affiliation: Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Faculty of Medicine, Kagawa University, 1750-1 Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
authors.forename: Kyuichi
authors.initials: K
authors.lastname: Kadota
authors.forename: Cheng-Long
authors.initials: CL
authors.lastname: Huang
authors.forename: Dage
authors.initials: D
authors.lastname: Liu
authors.forename: Nariyasu
authors.initials: N
authors.lastname: Nakashima
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Yokomise
authors.forename: Masaki
authors.initials: M
authors.lastname: Ueno
authors.forename: Reiji
authors.initials: R
authors.lastname: Haba
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry*; D058846:Antibodies, Monoclonal, Murine-Derived; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008175:Lung Neoplasms / Q000098:blood supply / Q000473:pathology*; D042583:Lymphangiogenesis; D008297:Male; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000473:pathology; D015996:Survival Rate
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; C500987:monoclonal antibody D2-40