| ObjectiveTo investigate the expression of NGAL, E-cadherin and MMP-9 and correlation with recurrence and metastasis in the colon carcinoma, and to further explore their interrelationship and the correlation between them and prognosis, and to preliminary study the mechanism of NGAL in the metastasis of colon carcinoma.MethodsClinical characteristics and prognosis of 227 colon carcinoma patients diagnosed between 2000 and 2004 were reviewed. The paraffin embedded tissues were selected and tissue micro array blocks were made (83 with recurrence and metastasis and 144 without recurrence and metastasis). Immunohistochemical staining was used to evaluate the expression of NGAL, MMP-9 and E-cadherin in colon carcinoma and to analyze its correlation with recurrence and metastasis in colon carcinoma.Results1. clinical cases data reviewIn 227 colon carcinoma cases, NM group had 83 cases and NRM group had 144cases. The mean survival time of patients in RM group was (32.710±2.360) months, and the median survival time of it was 25 months. The mean survival time of patients was (62.454±2.821) months and the median survival time was 73 months in NRM group. Recurrence and metastasis was closely related to lymph nodes metastasis, pathological grade, clinical stage, chemotherapy. Patients with lymph nodes metastasis have more possibility to recurrence and metastasis than those without lymph nodes metastasis (X2=116.3, P=0.000). The higher the pathological grade, the higher the possibility of recurrence and metastasis (X2=18.611, P<0.000) The later the clinical stage, the higher the possibility of recurrence and metastasis (X2=149.6, P=0.000). Patients with chemotherapy have more possibility to recurrence and metastasis than those without chemotherapy (X2=7.435, P=0.006). Recurrence and metastasis was unrelated with gender, age, site, size, invasion depth, radiotherapy (X2=0.344, P=0.558; X2=3.336, P=0.068; X2=0.042, P=0.837; X2=0.005, P=0.943; X2=2.594, P=0.107; X2=2.031, P=0.154)Survival time was closely related to lymph nodes metastasis, clinical stage, recurrence and metastasis. Survival time of patients with lymph nodes metastasis was shorter than those without lymph nodes metastasis (P=0.000). The later the clinical stage, the shorter the survival time (P=0.000). Survival time of patients with recurrence and metastasis was shorter than those without recurrence and metastasis (P=0.000). Survival time was unrelated with gender, age, site, size, invasion depth, pathological grade, radiotherapy, chemotherapy (P=0.969; P=0.406; P=0.131; P=0.580; P=0.531; P=0.067; P=0.333; P=0.207)2. the expression of NGAL,E-cadherin,MMP-9 in colon carcinoma and their correlation with recurrence and metastasis2.1 Immunohistochemical expression of NGAL:NGAL was mainly expressed in cytoplasm of the colon carcinoma, extensively, showing brown. We discovered that the difference of NGAL in the cytoplasm between the two groups had statistical significance. The expression of NGAL-cytoplasm in RM group was higher than that in NRM group (Z=-2.150,P=0.032). The expression of NGAL was closely related to lymph nodes metastasis, recurrence and metastasis, clinical stage. The expression of NGAL in patients with lymph nodes metastasis was higher than those without lymph nodes metastasis (X2=5.080, P=0.024). The expression of NGAL in patients with recurrence and metastasis was higher than those without recurrence and metastasis (X2=5.361, P=0.021).The later the clinical stage, the higher the expression of NGAL (X2=5.706, P=0.017). The expression of NGAL was unrelated with gender, age, site, size, invasion depth, pathological grade, clinical stage, radiotherapy, chemotherapy (X2=1.002, P=0.317; X2=0.012, P=0.914; X2=0.243, P=0.622; X2=0.135, P=0.713; X2=0.033, P=0.857; X2=0.571, P=0.450; X2=0.376, P=0.540; X2=0.459, P=0.498)2.2 Immunohistochemical expression of E-cadherin:E-cadherin was mainly expressed in membrane and cytoplasm of the colon carcinoma, extensively, showing brown. We discovered that the difference of E-cadherin in the membrane and cytoplasm between the two groups had statistical significance. The expression of E-cadherin in RM group was lower than that in NRM group (Z=-2.164,P=0.030) The expression of E-cadherin was closely related to age, lymph nodes metastasis, pathological grade, recurrence and metastasis, clinical stage, radiotherapy. The expression of NGAL in patients more than 59 years old was higher than those less than 59 years old(X2=5.727, P=0.017). The expression of E-cadherin in patients with lymph nodes metastasis or recurrence and metastasis was lower than those without lymph nodes metastasis or recurrence and metastasis (X2=6.000, P=0.014; X2=4.002, P=0.045). The higher the pathological grade, the lower the expression of E-cadherin (X2=13.892, P=0.000). The later the clinical stage, the lower the expression of E-cadherin (X2=3.943, P=0.047). The expression of E-cadherin in patients with radiotherapy was higher than those without radiotherapy (X2=4.854, P=0.028). The expression of E-cadherin was unrelated to gender, site, size, invasion depth, chemotherapy (X2=0.294, P=0.588; X2=2.090, P=0.148; X2=0.036, P=0.849; X2=2.456, P=0.117; X2=3.515, P=0.061)2.3 Immunohistochemical expression of MMP-9:MMP-9 was mainly expressed in cytoplasm of the colon carcinoma, showing brown. We discovered that the difference of MMP-9 in the cytoplasm between the two groups had statistical significance. The expression of MMP-9 in RM group was higher than that in NRM group (Z=-3.735,P=0.000). The expression of MMP-9 was closely related to size, recurrence and metastasis. The bigger the tumor, the higher the expression of MMP-9 (X2=4.435, P=0.035). The expression of MMP-9 in patients with recurrence and metastasis was higher than those without recurrence and metastasis (X2=4.017, P=0.045). The expression of MMP-9 was unrelated to gender, age, site, invasion depth, lymph nodes metastasis, pathological grade, clinical stage, radiotherapy, chemotherapy (X2=0.346, P=0.556; X2=0.015, P=0.902; X2=1.919, P=0.166; X2=0.002, P=0.967; X2=0.263, P=0.608; X2=0.150, P=0.699; X2=0.999, P=0.318; X2=0.666, P=0.414; X2=3.225, P=0.073)3.correlation between NGAL,E-cadherin and MMP-9 and prognosisThe Kaplan-Meier survival analysis showed that the difference of the survival time between the positive and negative group about NGAL-cytoplasm E-cadherin-membrane/cytoplasm,MMP-9-cytoplasm had statistical significance. The survival time of the positive groups about NGAL, MMP-9 was shorter than that of the negative group (P=0.000,P=0.010), and the survival time of the positive group about E-cadherin was longer than that of the negative group (P=0.000)Conclusion1. Recurrence and metastasis were closely related to lymph nodes metastasis, pathological grade, clinical stage, chemotherapy. Patients with lymph nodes metastasis have more possibility to recurrence and metastasis than those without lymph nodes metastasis. The higher the pathological grade, the higher the possibility of recurrence and metastasis. The later the clinical stage, the higher the possibility of recurrence and metastasis. Patients with chemotherapy have more possibility to recurrence and metastasis than those without chemotherapy. Recurrence and metastasis was unrelated with gender, age, site, size, invasion depth, radiotherapy.Survival time was closely related to lymph nodes metastasis, clinical stage, recurrence and metastasis. Survival time of patients with lymph nodes metastasis was shorter than those without lymph nodes metastasis. The later the clinical stage, the shorter the survival time. Survival time of patients with recurrence and metastasis was shorter than those without recurrence and metastasis. Survival time was unrelated with gender, age, site, size, invasion depth, pathological grade, radiotherapy, chemotherapy.2. NGAL was able to down-regulate E-cadherin expression. Decreasing or missing expression of E-cadherin may induce the missing of colon carcinoma cell polarity, intercellular adhesion descend, and promote recurrence and metastasis.3. NGAL was able to adjust the activity of these compounds. Most of the time, NGAL played the role of protecting MMP-9 which decline matrix outside of cell and promote recurrence and metastasis. |
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