title: High serum alkaline phosphatase cooperating with MMP-9 predicts metastasis and poor prognosis in patients with primary osteosarcoma in Southern China.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 1st Affiliated Hospital of Sun Yat-sen University, Pathological Department, Guangzhou, P R China.
authors.forename: Ju
authors.initials: J
authors.lastname: Han
authors.forename: Bicheng
authors.initials: B
authors.lastname: Yong
authors.forename: Canqiao
authors.initials: C
authors.lastname: Luo
authors.forename: Pingxian
authors.initials: P
authors.lastname: Tan
authors.forename: Tingsheng
authors.initials: T
authors.lastname: Peng
authors.forename: Jingnan
authors.initials: J
authors.lastname: Shen
mesh_terms: D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D001859:Bone Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology; D002648:Child; D002681:China; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000097:blood* / Q000401:mortality / Q000556:secondary; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D012516:Osteosarcoma / Q000097:blood* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D000469:Alkaline Phosphatase; D020780:Matrix Metalloproteinase 9