| ObjectiveTo study the expression of matrix metalloproteinase-2 (MMP-2) and to examine the lymphatic genesis with vascular growth factor 3 (VEGFR-3) as the marker of lymphatic vessel endothelial cells in human esophageal squamous carcinoma tissue, and to study the relationship between tumor expression of MMP-2 and lymphatic genesis.MethodsWe collected 431 post-surgical esophageal squamous carcinoma cases in Taian Central Hospital from 2004 to 2008 with complete clinical and pathologi-cal profiles and well-preserved samples in paraffin blocks. The experimental group was comprised of 100 randomly-selected cases all confirmed by pathological examination without pre-surgical radiation and chemotherapy.20 cases of normal esophageal tissue at least 5cm away from the tumors were collected as the control group. We stained both groups with hematoxylin and eosin (HE) method and immunohistochemistry(SP) method, and detected the expression of MMP-2,VEGFR-3 and lymphatic density (LVD).Results1. Clinical DataThere were 79 males and 21 females ir:100 cases of esophageal squamous cell carcinoma, the male/female ratio was 3.8:1; the patients'age was 41-80 years,58.55 in average; Histological grading:37 cases of high differentiation, 33 of middle differentiation, and 30 of low differentiation; 70 cases had lymph node metastasis and 30 cases had not. They were mostly diagnosed and admitted for dysphagia or retrosternal discomfort. 2. The Expression of MMP-2No positive expression of MMP-2 was observed in the normal esophageal mucosa tissue, whereas in esophageal squamous cell carcinoma was 64%. The difference was statistically significant compared with the normal esophageal tissue (χ2= 27.43, P<0.05).The rate of positive expression of MMP-2 in lymph node-positive group and negative group were 82.9% and 20.0% respectively, the difference was statistically significant between the two groups (χ2= 5.36, P<0.05).The Spearman correlation analysis showed a positive correlation between MMP-2 expression and lymph node metastasis (r=0.57, P<0.05). In this study we did not find the correlation between the expression of MMP-2 and age, gender or the degree of differentiation of cancer tissue.3. The Lymphantic GenesisSingle and cluster of endothelial cells, in which VEGFR-3 are positive, could be seen in tissues of ESC. Meanwhile, gradually formed fissure and lumen structures were also observed. Monolayer of endothelial cells composed of the thin vessel wall. No erythrocyte but sporadic cancer emboluses were discovered in the lumens. Based on these characteristics which only present simutaneously in lymphatics, the fissure and lumen structures were confirmed as neogenesis lymphatic vessels. The VEGFR-3 vessel number in esophageal squamous cell carcinoma was 4.12±1.76/high power field (HPF), and in normal tissues 1.62±0.07/HPF. The difference was statistically significant (t=6.20, P<0.05), which suggested the lymphantic genesis in esophageal cancer lymphatic vessels was more easily. The VEGFR-3 positive vessel number in MMP-2 positive group,5.02±2.24/HPF, was significantly higher than that in MMP-2 negative group (2.82±0.16/HPF, P<0.05), indicating that MMP-2 positive group was much easier in generating VEGFR-3 positive vessels. LVD were 4.26±2.72 in MMP-2 positive group and 2.00±1.46 in MMP-2 negative group; 4.75±2.52 in positive lymph node metastasis group and 1.50±1.03 in negative lymph node metastasis group; the differences within were both statistically significant (P<0.05), Suggesting the ESC tissues are more likely to induce generation of lymphatic vessle compared with normal tissues because of the highly expressed MMP-2 and VEGFR-3 generated in the former, and therefore the carcinoma cell metastasis are promoted. LVD was positively correlated with MMP-2 expression (r=0.66, t=2.53, P<0.05) as well as with lymph node metastasis (r=0.397, t =4.53, P<0.05) according to the Spearman correlation analysis.Conclusion1. MMP-2 was significantly expressed in sophageal squamous carcinoma tissue.2. MMP-2 may induce lymphatic genesis and facilitate metastasis.3. MMP-2 could be an important marker for the progress of esophageal squamous carcinoma. |
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