Differential Expression Of MMP-9,uPA And UPAR And Prognostic Factors In Esophageal Squamous Cell Carcinoma Treated By Radiotherapy

Objective: To investigate the differential expression of MMP-9,uPA and uPAR and prognostic factors in esophageal squamous cell carcinoma treated by radiotherapy.Methods: From February 2002 to August 2004, 59 specimens of esophageal squamous cell carcinoma(ESCC) and 41 specimens of peri-carcinoma tissues were collected. Each patient received definitive radiotherapy. Among them, male 36, female 23, median age 63(37~82y), local lesion length less than 5.0 cm in 23 cases, more than 5.0 cm in 36 cases. The cases of stageâ… ,â…¡,â…¢andâ…£were 2, 29, 22 and 6 respectively according to the criteria of tumor status in esophageal carcinoma. 39 patients accepted conventional radiotherapy (CRT), 2 Gy per day, 5 fractions per week, radiotherapy was given with 6MV-X ray, 13 patients accepted 3D Conformal Radiation Therapy(3DCRT), and other 7 patients accepted 3D Conformal Radiation Therapy(3DCRT) in the latter course. They accepted total doses of 50~70Gy, median doses of 60 Gy. MMP-9,uPA and uPAR protein was measured in all specimens with immunohistochemistry.Results: (1) The expression of MMP-9,uPA and uPAR protein in esophageal carcinoma and the peri-carcinoma tissues: The rates of positive expression of MMP-9 in esophageal carcinoma and the peri-carcinoma tissues were 84.75%(50/59)and 39.02%(16/41)respectively, and between the two groups there was significantly difference(P<0.01). The rates of positive expression of uPA in esophageal carcinoma and the peri-carcinoma tissues were 76.27%(45/59)and 48.78%(20/41)respectively, and between the two groups there was significantly difference(P<0.01). The rates of positive expression of uPAR in esophageal carcinoma and the peri-carcinoma tissues were 77.97%(46/59)and 43.90%(18/41)respectively, and between the two groups there was significantly difference(P<0.01). (2) The relationship of MMP-9,uPA and uPAR protein expression in esophageal carcinoma: there were clearly positive correlations between MMP-9 and uPA expression (P=0.003), MMP-9 and uPAR expression (P=0.003), uPA and uPAR expression (P=0.000). (3) The correlation between MMP-9,uPA and uPAR protein expression and the clinicopathological parameters:The expression of MMP-9 was significant correlated with the depth of tumor invasion in CT image.The rates of positive expression of MMP-9 was 78.57% (33/42) in which the depth of tumor invasion no more than 2 cm,while it was 100% (17/17) in which more than 2 cm, and this difference had statistical significance (P=0.048) . The expression of uPA was significant correlated with the status of fat interspace between vertebra, The rates of strong positive expression was 43.75% (14/32) in which the fat interspace existed, while it was 70.37% (19/27) with the fat interspace elapsed. This difference had statistical significance (P=0.040). The expression of uPA was significant correlated with distant metastasis, The rates of positive expression was 100%(14/14) in those distant metastasis took place ,while it was 68.89%(31/45) with no distant metastasis, the difference had statistical significance (P=0.042). No significant correlation were shown between MMP-9,uPA and uPAR protein expression and the other clinicopathological parameters, such as T stage,N stage,clinical stage,lymphanode metastasis. (4) The evaluation in short-term result after radiotherapy of esophageal carcinoma: CR 54.24% (32/59), PR 45.76% (27/59), CR+PR 100%. The 1,2,3-year survival rates and median were 55.93%, 38.98%, 28.41% and 15 months respectively. The expression of MMP-9,uPA and uPAR did not significantly effect on the short-term result of esophageal carcinoma.(5)The analysis of prognostic factors in esophageal carcinoma: As shown by univariate analysis, the age,hoarse voice,local lesion length in X,T,N and clinical stage were significantly correlated with patient survival. T,N were identified as independent prognostic factors by multivariate.Conclusion: MMP-9,uPA and uPAR expression in esophageal carcinoma was significantly higher than that in peri-carcinoma tissues, and there were significant correlations among the expression of MMP-9,uPA and uPAR. The expression of MMP-9,uPA were correlated with tumor invasion. The expression of MMP-9,uPA and uPAR did not significantly influnce on the short-term curative effect of esophageal carcinoma. As shown by univariate analysis, the age,hoarse voice,local lesion length in X,T,N and clinical stage were significantly correlated with patient survival. T,N were identified as independent prognostic factors.