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

✍ Scribed by Akihiko Takeuchi; Yasuhiko Yamamoto; Koichi Tsuneyama; Chunmei Cheng; Hideto Yonekura; Takuo Watanabe; Katsuji Shimizu; Katsuro Tomita; Hiroshi Yamamoto; Hiroyuki Tsuchiya


Publisher
John Wiley and Sons
Year
2007
Tongue
English
Weight
393 KB
Volume
109
Category
Article
ISSN
0008-543X

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✦ Synopsis


Abstract

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.