title: Nuclear localization of B7-H4 in pulmonary adenocarcinomas presenting as a solitary pulmonary nodule.
abstract: OBJECTIVE
  Although the pathogenicity of B7-H4 in cancer is well established, its role in pulmonary adenocarcinoma, especially lesions presenting as solitary pulmonary nodules (SPNs), remains unclear.
  
  
  METHODS
  40 cases of pulmonary adenocarcinoma presenting with SPN were enrolled during year 2012-2015. The B7-H4 expression and its subcellular distribution in pulmonary adenocarcinoma presenting with SPN were analyzed by immunohistochemistry, further its correlation with Ki-67 expression and CT feature. In vitro, the B7-H4 expression in the cytoplasmic and nucleus fractions of lung cancer cell lines was determinate by western blotting.
  
  
  RESULTS
  Immunostaining revealed B7-H4 in the cytoplasm of cells from all 40 SPN samples studied. No surface localization of B7-H4 was detected, but in 18 samples the nuclear membranes were B7-H4-positive. Moreover, patients with more poorly differentiated and invasive adenocarcinomas showed greater localization of B7-H4 to the nuclear membrane. The percentage of lesions with ground-glass opacity was significantly greater among samples negative for nuclear membrane B7-H4. Most importantly, there was a statistically significant relationships between the Ki-67 index and B7-H4 positivity of the nuclear membrane. This suggests tumors exhibiting higher nuclear membrane B7-H4 have greater proliferative potential. Western blotting confirmed both cytoplasmic and nuclear B7-H4 localization in lung adenocarcinoma cell lines.
  
  
  CONCLUSIONS
  Taken together, our study provides a new insight into the tumorigenicity of B7-H4 in lung adenocarcinoma. We suggest that in pulmonary adenocarcinoma presenting with SPN, nuclear membrane localization of B7-H4 within the tumor cells is associated with increased malignancy.
authors.affiliation: Respiratory Department, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Chen
authors.affiliation: Pathology Department, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Zhu
authors.affiliation: Pathology Department, Soochow University, Suzhou, 215006, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Xie
authors.affiliation: Respiratory Department, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
authors.forename: Jian-An
authors.initials: JA
authors.lastname: Huang
mesh_terms: D000072283:A549 Cells; D000230:Adenocarcinoma / Q000175:diagnosis / Q000378:metabolism*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008175:Lung Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D003074:Solitary Pulmonary Nodule / Q000175:diagnosis / Q000378:metabolism*; D019616:Thoracic Surgical Procedures; D013908:Thoracotomy; D014057:Tomography, X-Ray Computed; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1 / Q000378:metabolism*
chemical_list: D019394:Ki-67 Antigen; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475826:VTCN1 protein, human
keywords: B7-H4; adenocarcinoma; ground-glass opacity; solitary pulmonary nodule