Immunohistochemical expression of RANKL, RANK, and OPG in human oral squamous cell carcinoma.
BACKGROUND
The mechanism of oral squamous cell carcinoma (SCC) invading jawbone remains controversial. Interactions between receptor activator of NF-kappaB (RANK) and its ligand (RANKL) are required for osteoclastogenesis. The binding of RANK and RANKL induces differentiation of osteoclasts, leading to bony destruction. Osteoprotegerin (OPG), a decoy receptor for RANKL, also binds to RANKL by competing with RANK, and this could protect against osseous destruction.


METHODS
Immunoexpression of RANKL, RANK, and OPG in 25 cases of human buccal SCCs without bony invasion and 15 cases of gingival SCCs with mandibular bony invasion was investigated. Normal oral mucosa from five individuals without betel-quid chewing or cigarette smoking was used as a control. The scores are designated as percentage of positive staining x intensity of staining for each section.


RESULTS
Strong cytoplasmic staining of RANKL proteins is detected in cancer cells of both buccal and gingival SCCs. The same protein is identified in cytoplasm of osteoclasts for all cases involving bony invasion. Strong cytoplasmic staining of RANKL is confined to basal layer for all normal mucosa. A similar staining pattern is noted for RANK protein in all buccal and gingival SCCs. An absence of staining of RANK protein is noted for all normal tissues. Weak to negative cytoplasmic stained OPG protein is present in all buccal and gingival SCCs, but is absent in all normal tissues.


CONCLUSIONS
These findings suggest the potential value of the RANK/RANKL/OPG pathway as biomarkers in human oral SCCs.
Chuang
Fu-Hsiung
FH
Department of Endodontics & Operative Dentistry, Faculty of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Hsue
Shue-Sang
SS
Wu
Chung-Wei
CW
Chen
Yuk-Kwan
YK
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002454:Cell Differentiation / Q000502:physiology; D004396:Coloring Agents; D003593:Cytoplasm / Q000648:ultrastructure; D005260:Female; D005887:Gingival Neoplasms / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008339:Mandibular Neoplasms / Q000473:pathology; D008875:Middle Aged; D009061:Mouth Mucosa / Q000473:pathology; D009062:Mouth Neoplasms / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010010:Osteoclasts / Q000473:pathology; D053244:Osteoprotegerin / Q000032:analysis*; D053245:RANK Ligand / Q000032:analysis*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000032:analysis*
D014408:Biomarkers, Tumor; D004396:Coloring Agents; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human