Increased cytoplasmic S100A6 expression is associated with pulmonary adenocarcinoma progression.

S100A6 is a calcium-binding protein implicated in many cellular processes and frequently upregulated in cancer. Recently it was reported that S100A6 is one of the genes having higher expression in adenocarcinoma mixed subtype with a bronchioloalveolar carcinoma (BAC) component than in pure BAC. To clarify the association of S100A6 expression with stepwise progression of lung adenocarcinoma, S100A6 protein expression was examined on immunohistochemistry in 92 formalin-fixed and paraffin-embedded lung adenocarcinomas. Both the nucleus and cytoplasm of the tumor cells were stained, and the nuclear and cytoplasmic expression of S100A6 was assessed individually. In addition, six frozen surgical specimens were selected, and the expression of S100A6 was confirmed on western blotting. As a result, although it was not possible to detect any significant correlation between nuclear S100A6 immunoreactivity and tumor progression, advanced adenocarcinoma had significantly higher cytoplasmic S100A6 expression than non-invasive lesions or normal lung tissue (P < 0.05). Moreover, the BAC component tended to have weaker staining than any of the other components. These findings indicate that S100A6 may be associated with the stepwise progression and/or invasion of lung adenocarcinoma, especially BAC-type adenocarcinoma. The present results suggest the utility of S100A6 immunohistochemistry as a marker for estimation of malignancy in adenocarcinoma with a BAC component.