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Receptor protein esRAGE linked to bone tumor metastasis
The RAGE variant is more prominent in chondrosarcoma than in enchondroma.
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A recently discovered protein receptor is prominent in certain malignant bone tumors and may even help physicians diagnose lung metastasis.
Lead author Akihiko Takeuchi, MD, of the departments of orthopedic surgery and biochemistry and molecular vascular biology at Kanazawa University Graduate School of Medical Science, Japan, said the interaction of RAGE and amphoterin/high-mobility group box 1 (HMGB1), a ligand for RAGE, is a known contributor to tumor metastasis.
More recently, researchers identified a soluble RAGE variant: endogenous secretory RAGE, or esRAGE, he said.
“This RAGE-variant protein is thought to be a factor modifying RAGE-associated malignant phenotypes,” Takeuchi told Orthopedics Today. “Until now, the expression of RAGE was reported in various types of cancer, such as prostate, lung, colon and breast cancer. But the expression of RAGE in bone tumors is not reported.”
Nor has esRAGE expression been reported in various cancer types, including bone tumors, he noted.
He and his colleagues sought a link between esRAGE expression and tumor malignancy, and cancer metastasis to the lungs. He presented his team's findings at the American Academy of Orthopaedic Surgeons 73rd Annual Meeting.
“As we know, to distinguish low grade chondrosarcoma from enchondroma is often difficult by only histological findings,” Takeuchi said. “In general, chondrosarcoma is recognized to present a slow growth and infrequently develops to metastasis and the prognosis is favorable. However, grade 1 chondrosarcoma occasionally progressed to lung metastasis.”
Measuring malignancy
Takeuchi and fellow researchers evaluated 24 cases of enchondroma and 39 cases of conventional chondrosarcoma (24 grade 1 cases, 13 grade 2 cases and two grade 3 cases). They used normal epiphyseal cartilage tissue as a control.
The study was 54.9 months long, and the patient group was 56.7% male and 43.3% female, with a mean age of 49 years.
Researchers found RAGE, esRAGE and HMGB1 proteins in normal epiphyseal cartilage, enchondroma and chondrosarcoma. They found esRAGE expression of 15.3% in normal epiphyseal cartilage, 35.1% ± 11.4% in enchondroma, 68.1% ± 11.8% in grade 1 chondrosarcoma, 78.7% ± 7.6% in grade 2 chondrosarcoma and 93.6% ± 2.2% in grade 3 chondrosarcoma.
The esRAGE labeling index was considerably higher in grade 1 chondrosarcoma than in enchondroma (P<0.01), and the esRAGE index also differed widely between grade 1 and grade 2 chondrosarcoma (P<0.01), Takeuchi said.
100% survival rate
The five-year survival rate was 100% in the low esRAGE group (<70%) and 65% in the high esRAGE group (>70%), Takeuchi said.
“The expression of esRAGE by immunohistochemistry and esRAGE protein concentration in tumor tissues showed a significant difference between enchondroma and grade 1 chondrosarcoma,” Takeuchi said. “Moreover, a high esRAGE level correlates with lung metastasis and cumulative survival rate. Accordingly, we consider that esRAGE would be a useful diagnostic marker and a predictor of lung metastasis and survival time in patients with chondrosarcoma.”
For more information:
- Takeuchi A, Tsuchiya H, Yamamoto Y, et al. Expression of esRAGE is associated with histological grade of malignancy in chondrosarcoma. Tumor. Paper #040. Presented at the American Academy of Orthopaedic Surgeons 73rd Annual Meeting. March 22-26. Chicago.