Expression of RANKL, RANK and OPG in human OSCC

Objectives: Oral squamous cell carcinoma (SCC)may invade locally the jaw bone but the exact mechanism of this remains controversial.The aim of the present work is to study the immunohistochemical expression of RANKL, RANK and OPG. Methods: Immunohistochemical expression of RANKL, RANK and OPG in 25 cases of human buccal SCCs without bony invasion and 15 cases of oral SCCs with multiple sites of mandibular invasion were investigated. Normal oral mucosa from five individuals without betel-quid chewing or cigarette smoking was used as a control. Results: Strong cytoplasmic staining of RANKL are detected in the cells of buccal SCCs without bony destruction and also of oral SCCs with bony destruction. The same protein is also identified in the cytoplasm of osteoclasts in all cases involving bony invasion. Furthermore, strong cytoplasmic staining of RANKL is confined to the basal cell layer of all cases of normal buccal mucosa. A similar staining pattern is noted for RANK in all specimens of buccal and oral SCCs studied. An absence of staining of RANK is noted for all the normal mucosal tissues. Conversely, weakly cytoplasmic stained OPG is present in all specimens of buccal and oral SCC but is not present in all specimens of normal mucosal tissue. The average total scores for both RANKL and RANK immunostainings were significantly higher than the average total score of OPG staining respectively for both SCCs with and without bony invasion (p < 0.001). The average total scores for RANKL, RANK and OPG immunostainings of SCCs with and without bony invasion were significantly higher than the average total score of the normal tissues (p < 0.001). Conclusions: These findings suggest that osseous destruction by SCC in the oral cavity appears to be mediated by the cancer cell itself through the activation of osteoclasts via a RANKL/RANK/OPG pathway.