The Clinical Significance Of TS,Bcl-2,Topo-Ⅱ Expression In Primary Colorectal Carcinomas And Their Corresponding Lymph Node Metastases

Objective:To investigate the changes of multidrug resistance during colorectal carcinoma metastasis and provide a theoretical basis for clinical individual chemotherapy of colorectal carcinomas, we detect the differences of the protein and mRNA levels of TS, Bcl-2, Topo-II and the apoptosis levels between colorectal carcinomas and their lymph nodes.Methods:1 Immunohistochemical and Tunel staining were performed to detect the expression of TS, Bcl-2, Topo-II protein and apoptosis index (AI) in the tissue microarrays of 135 colorectal cancer tissues and 60 lymph node metastasis tumors.2 Western Blotting,Real-time PCR and flow cytometry were performed to detect the expression of TS, Bcl-2, Topo-II protein,mRNA and apoptosis levels in SW480 and SW620 colon carcinoma cells.Results:1 There was no significant difference in TS positive expression rate between colorectal carcinomas tissues(54.8%) and peritumor tissues (43.0%) (P>0.05).The positive expression of Bcl-2 in peritumor tissues(39.3%) was significantly higher than that in colorectal carcinomas tissues(27.4%) (P<0.05).The positive expression of Topo-II in colorectal carcinomas tissues(53.3%) was significantly higher than that in peritumor tissues(21.4%) (P<0.05). The positive expression of Bcl-2 protein in well or moderately differentiated colorectal carcinomas was significantly higher than that in poorly differentiated colorectal carcinomas (P<0.05). The positive expression of Topo-Ⅱprotein in moderately differentiated colorectal carcinomas was significantly higher than that in well differentiated colorectal carcinomas (P<0.05). The positive expression of TS, Bcl-2, Topo-Ⅱin 60 primary colorectal carcinomas were 53.3%,31.7%,56.7%, and in the matched lymph node metastasis were 41.7%,16.7%,31.7%, respectively. The positive expression of Topo-Ⅱin 60 primary colorectal carcinomas was significantly higher than that in the matched lymph node metastases (P<0.05). The expression conformation rate of TS, Bcl-2, Topo-Ⅱin primary colorectal carcinomas and matched lymph node metastases were 51.7%,55.0%,51.7%, respectively.2 The level of apoptosis index in colorectal carcinomas(5.66±1.85) was significantly higher than that in lymph node metastases(2.37±2.27) and was significantly lower than that in peritumor tissues(7.97±3.25) (P<0.05).3 The mRNA and protein expression of TS and Bcl-2 were significantly increased in SW480 cell as compared with those in SW620 cell (P<0.05). The expression of Topo-Ⅱprotein in SW480 cell was higher than that in SW620 cell (P<0.05).4 The early apoptosis rate was significantly higher in SW480 cell(2.57±0.57)% than that in SW620 cell(1.37±0.40)%(P<0.05).Conclusion:1 In primary colorectal carcinoma and metastatic lymph nodes, low expression conformation rate of TS, Bcl-2, Topo-II indicates a heterogeneity between them, which leads to multidrug resistance phenotype changes. Thus the combined detection of TS, Bcl-2, Topo-Ⅱin primary colorectal carcinoma and corresponding lymph node metastases enabled us to design individuality chemotherapy plan.2 The expression of TS, Bcl-2, Topo-ⅡmRNA and protein were higher in SW480 than in SW620 cell, which verifies the differences of three genes between primary colorectal carcinoma and metastatic lymph nodes in molecular biological level. It provided a theoretical basis to investigate multidrug resistance in colorectal carcinoma.3 The apoptosis level and Bcl-2 expression level are different in primary colorectal carcinoma and metastatic lymph nodes in histological, cellular, and molecular biological level, this detail mechanism needs to be further discussed.4 The SW480 and SW620 cells, which are originated from primary colon carcinoma and metastatic lymph node of a patient, respectively, provide an ideal cell model in vitro to further investigate multidrug resistance phenotype changes during colorectal carcinoma metastasis.