Endogenous secretory receptor for advanced glycation endproducts as a novel prognostic marker in chondrosarcoma

BACKGROUND Chondrosarcoma, the second most frequent primary malignant bone tumor, is classified into 3 grades according to histologic criteria of malignancy. However, a low‐grade lesion can be difficult to distinguish from a benign enchondroma, whereas some histologically low‐grade lesions may carry a poor prognosis. The receptor for advanced glycation endproducts (RAGE) and its ligand, high‐mobility group box‐1 (HMGB1), was quantified in enchondromas and chondrosarcomas to determine whether these markers were associated with histological malignancy and prognosis. METHODS Enchondromas (n = 20) and typical chondrosarcomas (n = 39) were evaluated for RAGE, endogenous secretory RAGE (esRAGE, a splice variant form), and HMGB1 protein expression by immunohistochemistry including laser confocal microscopy. The content of esRAGE in resected specimens was measured with an enzyme‐linked immunosorbent assay. Associations of these molecules with histology and clinical behavior of tumors were analyzed. RESULTS Expression of esRAGE and HMGB1 was observed in all specimens. The numbers of cells positive for esRAGE and HMGB1 expression were positively associated with histologic grade. Expression of esRAGE was significantly higher in chondrosarcomas than in enchondromas (P < .001). Tissue esRAGE content was also significantly higher in grade 1 and 2 chondrosarcomas than enchondromas (P = .0255 and P = .008, respectively). High expression of esRAGE in grade 1 chondrosarcoma was associated with subsequent recurrence (P = .0013), lung metastasis (P = .0071), and poor survival (P < .001). CONCLUSIONS Assessment of esRAGE expression should aid in diagnostic andprognostic determinations in chondrosarcoma. Cancer 2007. © 2007 American Cancer Society. The receptor for advanced glycation endproducts (RAGE) is a multiligand receptor that has been implicated in diabetic vascular complications, neurodegenerative disorders, proinflammatory reactions, and cancer. The study revealed that the expression of endogenous secretory RAGE (esRAGE, a splice variant form of RAGE) was associated with histologic tumor grade and clinical behavior in chondrosarcoma, the second most frequent primary malignant bone tumor. Assessment of esRAGE expression is useful in diagnostic and prognostic determinations in chondrosarcoma.