title: Microvessel density: correlation with 18F-FDG uptake and prognostic impact in lung adenocarcinomas.
abstract: Although researched for many years, the prognostic value of tumor angiogenesis reflected by microvessel density (MVD) is still controversial, and there have been no previous reports regarding the correlation with 18F-FDG uptake in lung adenocarcinomas. Therefore, in the present study, we investigated the correlation between MVD determined with different endothelial cell antibodies and 18F-FDG uptake and compared the prognostic impact of those factors in lung adenocarcinomas.
  
  
  METHODS
  Forty-four patients with 45 lung adenocarcinomas underwent 18F-FDG PET before surgery. Consecutive paraffin-embedded sections obtained from each resected tumor were immunostained for CD31 (a panendothelial cell marker), CD105 (a proliferation-related endothelial cell marker), and CD34/alpha-SMA (for double labeling of endothelial cells and mural cells). Four high-power fields in the area with the highest MVD were selected for analysis. Computer-assisted image analysis was used to assess MVD.
  
  
  RESULTS
  MVD staining results for panendothelial cell markers can be classified into 3 microvessel patterns: diffuse, alveolar, and mixed. The highly ordered alveolar pattern is believed to represent preexisting alveolar vessels trapped in lung adenocarcinomas and may have no significant meaning for the aggressiveness of tumors. Preexisting alveolar cells also do not contribute to 18F-FDG uptake. CD105 staining of MVD (CD105-MVD) showed a significantly positive correlation with 18F-FDG uptake (P < 0.0001), whereas CD31 staining of MVD (CD31-MVD) showed a marginally negative correlation with it (P = 0.057). Although CD105-MVD correlated negatively with prognosis, patients with low CD105-MVD, compared with those with high or moderate CD105-MVD, had a much better prognosis in both disease-free and overall survival analyses (P = 0.017 and P = 0.013, respectively). Patients with low CD31-MVD had the worst prognosis (P = 0.032 for disease-free survival analysis and P = 0.179 for overall survival analysis).
  
  
  CONCLUSIONS
  There is no positive correlation between 18F-FDG uptake and MVD determined with panendothelial cell markers (CD31 and CD34); in contrast, there is a marginally negative correlation between them. MVD determined with CD105, which is a proliferation-related endothelial cell marker, reflects active angiogenesis, correlates positively with 18F-FDG uptake, and is a better indicator of prognosis in lung adenocarcinomas.
authors.affiliation: Department of Radiology, Kanazawa Medical University, Ishikawa, Japan.
authors.forename: JianFei
authors.initials: J
authors.lastname: Guo
authors.forename: Kotaro
authors.initials: K
authors.lastname: Higashi
authors.forename: Yoshimichi
authors.initials: Y
authors.lastname: Ueda
authors.forename: Manabu
authors.initials: M
authors.lastname: Oguchi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takegami
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Toga
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Sakuma
authors.forename: Hajime
authors.initials: H
authors.lastname: Yokota
authors.forename: Shogo
authors.initials: S
authors.lastname: Katsuda
authors.forename: Hisao
authors.initials: H
authors.lastname: Tonami
authors.forename: Itaru
authors.initials: I
authors.lastname: Yamamoto
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000401:mortality*; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008175:Lung Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000401:mortality*; D008297:Male; D008833:Microcirculation / Q000000981:diagnostic imaging* / Q000378:metabolism; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000401:mortality*; D011379:Prognosis; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013223:Statistics as Topic
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18