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 and prognostic determinations in chondrosarcoma.
Takeuchi
Akihiko
A
Department of Orthopaedic Surgery, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
Yamamoto
Yasuhiko
Y
Tsuneyama
Koichi
K
Cheng
Chunmei
C
Yonekura
Hideto
H
Watanabe
Takuo
T
Shimizu
Katsuji
K
Tomita
Katsuro
K
Yamamoto
Hiroshi
H
Tsuchiya
Hiroyuki
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology; D002812:Chondroma / Q000378:metabolism* / Q000473:pathology; D002813:Chondrosarcoma / Q000378:metabolism* / Q000473:pathology; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism; D024243:HMGB1 Protein / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D015996:Survival Rate
D014408:Biomarkers, Tumor; D017127:Glycation End Products, Advanced; D024243:HMGB1 Protein; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic