Altered expressions of
receptor for advanced glycation end-products (RAGE) and its
ligand (S100A9) are observed in many
cancers and play a key role in
inflammation-associated
cancer. In our previous study, by two-dimensional gel electrophoresis followed by mass spectrometry, the expression of
S100A9 protein was found to increase in squamous
cervical cancer compared with adjacent normal cervical tissues. Therefore, in the present study we observed the expressions of S100A9 and RAGE in 30 chronic
cervicitis, 50
cervical intraepithelial neoplasia (CIN), and 40 squamous
cervical cancer (SCC) using immunohistochemical analysis and analyzed the differential expression and possible role of S100A9 and RAGE in
cancer development. Immunohistochemical findings were as follows: the expressions of S100A9 and RAGE were demonstrated in chronic
cervicitis, CIN, and SCC. Moreover, their expressions were gradually increasing as the
tumor progressed. In SCC, the staining scores of S100A9 and RAGE were significantly higher in well-differentiated
tumors compared to moderately and poorly differentiated
tumors. The expression of S100A9 in epithelial cells exhibited a positive correlation to RAGE expression in chronic
cervicitis, CIN, and SCC. There were no significant difference of S100A9 immunoreactivity in stromal cells among chronic
cervicitis, CIN, and SCC. Moreover, there was no correlation between S100A9 immunoreactivity in stromal cells of SCC and clinicopathological parameters. Finally, double immunohistochemistry illustrated that RAGE and S100A9 co-express in SCC. In conclusion, RAGE binds its
ligand (S100A9), which plays an important role in the development of SCC. In addition, the expressions of S100A9 and RAGE in SCC
tumor cells were closely associated with histological differentiation.