Nuclear localization of B7-H4 in pulmonary adenocarcinomas presenting as a solitary pulmonary nodule.
PURPOSE
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.
['Chen|Cheng|C|', 'Zhu|Wei-Dong|WD|', 'Xie|Fang|F|', 'Huang|Jian-An|JA|']
D000072283:A549 Cells D000230:Adenocarcinoma D000077192:Adenocarcinoma of Lung D000328:Adult D000368:Aged D045744:Cell Line, Tumor D002467:Cell Nucleus D003593:Cytoplasm D005260:Female D006801:Humans D007150:Immunohistochemistry D019394:Ki-67 Antigen D008175:Lung Neoplasms D008297:Male D008875:Middle Aged D003074:Solitary Pulmonary Nodule D019616:Thoracic Surgical Procedures D013908:Thoracotomy D014057:Tomography, X-Ray Computed D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1
B7-H4 adenocarcinoma solitary pulmonary nodule ground-glass opacity