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Endogenous secretory receptor for advanced glycation endproducts as a novel prognostic marker in chondrosarcoma
Author(s) -
Takeuchi Akihiko,
Yamamoto Yasuhiko,
Tsuneyama Koichi,
Cheng Chunmei,
Yonekura Hideto,
Watanabe Takuo,
Shimizu Katsuji,
Tomita Katsuro,
Yamamoto Hiroshi,
Tsuchiya Hiroyuki
Publication year - 2007
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.22731
Subject(s) - enchondroma , medicine , chondrosarcoma , malignancy , immunohistochemistry , pathology , rage (emotion) , biology , neuroscience
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.