title: Evaluation of MMP-9 and MMP-2 and their suppressor TIMP-1 and TIMP-2 in adenocarcinoma of esophagogastric junction.
abstract: OBJECTIVE
  Adenocarcinoma of esophagogastric junction (AEG) is a lethal malignancy featured with early metastasis, poor prognosis, and few treatment options. Matrix metalloproteinase (MMP) and metalloproteinase suppressor (TIMP) have been considered to be associated with cancer invasion and metastasis. In our study, we evaluated expressions of MMP-9, MMP-2, TIMP-1, and TIMP-2 in AEG and their correlation with clinicopathological parameters and the overall survival rate.
  
  
  METHODS
  Expressions of MMP-9, MMP-2, TIMP-1, and TIMP-2 in specimens from 120 AEGs were detected by immunohistochemistry. The correlations between expressions of these four proteins and clinicopathological characters were analyzed by chi-square test. Moreover, the prognostic value of these four biomarkers was evaluated by univariate analysis with Kaplan-Meier method and multivariate analysis with Cox regression model.
  
  
  RESULTS
  The positive expression rate of MMP-9, MMP-2, TIMP-1, and TIMP-2 was 65%, 53%, 70%, and 49%, respectively, in the detected 120 AEG samples. MMP-9 was significantly associated with poorly histological differentiation (P=0.001), lymph node metastasis (P=0.007), and UICC stage (P=0.008). TIMP-1 showed significantly reversed correlations with histological differentiation (P=0.001), lymph node metastasis (P=0.007), and Union for International Cancer Control stage (P=0.008). Univariate analysis revealed that lymph node metastasis (P=0.002), depth of invasion (P=0.050), and MMP-9+/TIMP-1 phonotype (P<0.001) were significantly associated with the overall survival rate. Multivariate analyses demonstrated that MMP-9+/TIMP-1-phenotype was an independent prognostic factor in AEGs.
  
  
  CONCLUSIONS
  Detection of MMP-9 and TIMP-1 expression allows stratification of AEG patients into different survival categories and can be useful for precise individual evaluation and survival prediction.
authors.affiliation: Department of General Surgery, Qilu Hospital of Shandong University; Department of General Surgery, Jinan Central Hospital of Shandong University.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Preventive Medicine, Jinan Central Hospital Affiliated to Shandong University.
authors.forename: Lingling
authors.initials: L
authors.lastname: Duan
authors.affiliation: Department of Gynecology and Obstetrics, Third People's Hospital of Jinan.
authors.forename: Hongqin
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Physical Examination, Second Hospital of Shandong University of Traditional Chinese Medicine.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Lu
authors.affiliation: Health Technology Exchange Center of Jinan.
authors.forename: Daolin
authors.initials: D
authors.lastname: Lu
authors.affiliation: Emergency Center of Jinan.
authors.forename: Daopeng
authors.initials: D
authors.lastname: Lu
authors.affiliation: Department of Pathology, Shandong University Medical School, Jinan, People's Republic of China.
authors.forename: Nan
authors.initials: N
authors.lastname: Jiang
authors.affiliation: Department of General Surgery, Qilu Hospital of Shandong University.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Chen
keywords: MMP-2; MMP-9; TIMP-1; TIMP-2; adenocarcinoma of esophagogastric junction; metastasis; prognosis