Abstract
PurposeAlthough 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.Methods40 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.ResultsImmunostaining 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.ConclusionsTaken 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.
Highlights
Solitary pulmonary nodules (SPNs) are single lesions in the lung that are ≤ 3 cm in diameter, without obstructive pneumonia or atelectasis involving lung segments or lobes
The percentage of lesions with ground-glass opacity was significantly greater among samples negative for nuclear membrane B7-H4
Taken together, our study provides a new insight into the tumorigenicity of B7-H4 in lung adenocarcinoma
Summary
Solitary pulmonary nodules (SPNs) are single lesions in the lung that are ≤ 3 cm in diameter, without obstructive pneumonia or atelectasis involving lung segments or lobes. In part to address recent advances in our understanding lung adenocarcinoma presenting as SPNs, new classifications were purposed by the relevant international multidisciplinary committees [1,2] According to those classifications, adenocarcinomas are classified as acinar, papillary, micropapillary, lepidic and solid. As the size and density of these malignant GGNs increased, their lepidic component gradually decreased, and were replaced www.impactjournals.com/oncotarget by acinar or papillary components [3,4]. This type of change in the composition of tumor cells is thought to be a specific feature of carcinogenesis [5]. The molecular changes in tumor composition during SPN growth has not been fully characterized
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