| Objective To explore the expression of coxsackie and adenovirus receptor (CAR) in bronchioloalveolar carcinoma (BAC), paraneoplastic tissue and normal tissue, analyze the correlation with carcinogenesis and development, as well as the different expression between different clinicopathologic parameter, and investigate the association of CAR with TGF-β1, Vimentin and E-cadherin.Methods Collecting BAC 36 samples, as well as its corresponding paraneoplastic tissue and normal tissue, put into liquid nitrogen as soon as removed from the patient's body,-80℃conserved. The expression of CAR protein was determined by Western blot. And adenocarcinoma Paraffin-embedded specimens and cases which were followed up completely for 3 years were obtained from 137 patients from 2002 to 2006. Immunohistochemical En Vision two-step method was used to detect the expression of CAR, TGF-β1, Vimentin and E-cadherin. And all data were analyzed using SPSS 13.0 statistics software and the Kaplan-Meier survival curve was constructed, meanwhile, we conducted a Log-rank test.Results1. The expression of CAR proteinBy Western blot, in the three groups of normal tissue, paraneoplastic tissue and carcinoma tissue, the expression of CAR was 0.891±0.144,1.057±0.193,1.220±0.269. There was a statistical significance in Carcinoma tissue, paraneoplastic tissue and normal tissue (P<0.05). In addition, it was a statistically significant difference between the expression of CAR and two of groups.2. The correlation of CAR expression with different clinicopathologic parameters.(1) CAR protein mainly located in the cell membrane, a small amount in the cytoplasm, no expression in the nucleus. In normal lung tissue, the positive rate of CAR was 13.3%; the positive rate of CAR in BAC was 71.5%, the difference was statistically significant difference (P<0.01). Meanwhile, between the group of BAC and other types of adenocarcinoma (AC) also had statistically significant differences.(2)There was no statistical significance in other clinicopathologic parameters, including gender, age, tumor size and T stage. The expression of CAR had significant difference both non-smoking and mucinous BAC (P<0.05). Among BAC patients of 137 cases,98 cases were positive, the average survival time of them was 33.03 months; 39 cases were negative, the average survival time of them was 31.90 months, overall survival of the two groups had no significance.3. The correlation between the expression of BAC and TGF-β1,Vimentin,E-cadherinSpearman rank correlation analysis showed that the expression of CAR had a negative correlation with the expression of TGF-β1 and Vimentin (P<0.01), and a positive correlation with the expression of E-cadherin (P<0.05).Conclusion1. In BAC, carcinoma tissue was statistically higher than lung normal tissue and paraneoplastic tissue. These data predicted that CAR expression might be necessary for the occurrence and development of human carcinoma, particularly for the formation of BAC.2. The expression of CAR had no significant difference among clinicopathologic parameters but between smoke or not and pathological classification had statiscal difference, in the mucinous BAC samples, CAR expression was higher than other types, which showed the expression of CAR in BAC was different from other types of lung cancer, more affected by environmental factors, and the formation of subtype closely, but the exact mechanism remained to be further studied.3. The higher expression of CAR in BAC for gene therapy with adenovirus (Ad) vectors has opened up a broader space; And in view of the conspicuous regulation of CAR, it may be a reliable evidence and bright future for gene therapy of other types of lung cancer.4. CAR protein had significantly negtive correlation between TGF-Bland Vimentin, positive correlation with E-cadherin. We might develop the TGF-βreceptor inhibition as EGFR-TKI. Enhancing the expression of CAR in tumor cells was benefit for further treatment of cancer.
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