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Evaluation of MMP-9 and MMP-2 and their suppressor TIMP-1 and TIMP-2 in adenocarcinoma of esophagogastric junction

Authors Lu X, Duan L, Xie H, Lu X, Lu D, Lu D, Jiang N, Chen Y

Received 31 October 2015

Accepted for publication 31 March 2016

Published 18 July 2016 Volume 2016:9 Pages 4343—4349


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Wei An

Peer reviewer comments 2

Editor who approved publication: Professor Min Li

Xiaofei Lu,1,2 Lingling Duan,3 Hongqin Xie,4 Xiaoxia Lu,5 Daolin Lu,6 Daopeng Lu,7 Nan Jiang,8 Yuxin Chen1

1Department of General Surgery, Qilu Hospital of Shandong University, 2Department of General Surgery, Jinan Central Hospital of Shandong University, 3Department of Preventive Medicine, Jinan Central Hospital Affiliated to Shandong University, 4Department of Gynecology and Obstetrics, Third People’s Hospital of Jinan, 5Department of Physical Examination, Second Hospital of Shandong University of Traditional Chinese Medicine, 6Health Technology Exchange Center of Jinan, 7Emergency Center of Jinan, 8Department of Pathology, Shandong University Medical School, Jinan, People’s Republic of China

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.
Conclusion: 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.

Keywords: adenocarcinoma of esophagogastric junction, MMP-9, MMP-2, TIMP-1, TIMP-2, metastasis, prognosis

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