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01.12.2012 | Research | Ausgabe 1/2012 Open Access

World Journal of Surgical Oncology 1/2012

High serum alkaline phosphatase cooperating with MMP-9 predicts metastasis and poor prognosis in patients with primary osteosarcoma in Southern China

World Journal of Surgical Oncology > Ausgabe 1/2012
Ju Han, Bicheng Yong, Canqiao Luo, Pingxian Tan, Tingsheng Peng, Jingnan Shen
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1477-7819-10-37) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

TP and JS conceived the study. JH and CL performed the staining. BY and PT collected the cases and clinical information. JH interpreted the staining results and performed the statistical analysis. JH performed the literature review and wrote the manuscript. All authors read and approved the final manuscript.



Osteosarcoma is a malignant tumor with high ability to form invasion and metastasis. Identifying prognostic factor in osteosarcoma is helpful to select those patients for more aggressive management. Our study evaluated serum alkaline phosphatase (ALP) cooperating with matrix metalloproteinase-9 (MMP-9) as an important prognostic predictor for local recurrence and distant metastasis of osteosarcoma.


177 cases were included from the osteosarcoma patients treated at 1st Affiliated Hospital of Sun Yat-sen University (1999-2008). Pre-chemotherapy serum ALP (pre-ALP) were studied and correlated with tumor recurrence, lung metastasis and patient survival. MMP-9 protein in tumor tissues was detected by immunohistochemistry and correlated with pre-ALP level.


Pre-ALP were partitioned into normal, high, and very high groups, in each group the incidence of metastases was 12.2%, 21.2% and 34.6%, respectively (p = 0.007). In the three groups the mean disease-free survival (DFS) was 57 ± 3.15, 28 ± 3.57 and 14 ± 3.35 months, respectively (p < 0.001); overall survival (OS) was 92 ± 26.89, 39 ± 8.61 and 17 ± 5.07 months, respectively (p < 0.001). By multivariate analysis, elevated serum pre-ALP were associated with shorter DFS (p = 0.018) and OS (p = 0.031). If elevated ALP levels decreased after clinical treatment, the incidence of lung metastasis rate decreased (p = 0.028); DFS and OS were both prolonged (p < 0.001). Pre-ALP was also positively correlated with MMP-9 expression (p = 0.015) in tumor tissue.


Pre-ALP was an independent prognostic factor for the survival of osteosarcoma patients in south China, and correlated with MMP-9 expression and lung metastasis. ALP can also serve as a prognostic marker for treatment, and merit large-scale validation studies.
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