The biological markers CXCR4, HER2 and CD44 are involved in tumor growth and the homing of cancer cells to distant sites. The aim of this retrospective, case-control study was to evaluate whether the expression of CXCR4, HER2 and CD44 correlated with poor prognosis. Expression levels of CXCR4, HER2 and CD44 were evaluated by immunohistochemical staining in paraffin-embedded tissue sections of malignant primary osteosarcoma and related metastatic carcinoma from 63 patients, at a median follow-up of 5.5 years (range 1-10 years). Associations between these parameters and clinical features were examined. Of the 63 specimens, there were 38 HER2‑positive, 57 CXCR4-positive and 62 CD44-positive cases. There were 36 cases of HER2 and CXCR4 co-expression, 38 cases of HER2 and CD44 co-expression and 56 cases of CXCR4 and CD44 co-expression. A total of 33 cases were CXCR4, HER2 and CD44 co-positive. Surface expression of CXCR4, HER2 and CD44 was high in the selected tissue samples, and CD44 was the most highly expressed. We observed a significant trend for a higher frequency of the expression of the three biomarkers in high-grade compared to low-grade osteosarcoma. Our results suggest a pivotal role of CXCR4, HER2 and CD44 expression as a prognostic factor of malignant human osteosarcoma. A larger study is ongoing to confirm these results.

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