Studies On Expression And Significance Of KISS-1 And KAI-1 In Gallbladder Carcinoma

Objective:To investigate the expression levels of the tumor metastasis-suppressor gene(Kiss-1 and KAI-1) in gallbladder carcinoma and their relationship with clinicopathologic parameters(type of tissue, differentiated degree,depth of infiltration and clinic stage)and metastasis potential.To find the significance of the two genes in the process of development of the metastasis of gallbladder carcinoma,and the possbile mechanisms of the metastasis of gallbladder carcinoma.Methods:Pathological specimens from 59 gallbladder carcinoma tissues(including 23 invasion tissues),matched 7 para-tumor and 6 nomal gallbladder tissues were examined for the expression of Kiss-1 and KAI-1 protein by tissue microarray technique and immunohisto-chemistry (EnVision).In the 59 patients of gallbladder carcinoma,there were 21 men and 38 women;And the mean age of patients was 63.7 years(＜60 years,21 examples;≥60 years,38 examples);And Adenocaiconoma,54 examples;Other types,5 examples(adenosquamous carcinoma,4 examples;Undifferentiated carcinoma,1 example);And invasion tissues(including metastasis of lymph node and invasion of liver) 23 examples.According to Nevin staging(1976),gallbladder carcinoma cases were divided into five stages(StageⅠ,5 examples,occuping 8.5%; StageⅡ,8 examples,occuping 13.6%;StageⅢ,21 examples,occuping 35.6%;StageⅣ,7 examples,occuping 11.9%;StageⅤ,18 examples, occuping 30.5%.).To observe the degree of staining and the range (percentage) of the positive cells in the patho-tissue microarray,then Chisq test,Fisher exact-propability test and Spearman rank correlation test were used for data statistic analysis by SPSS 11.0(size of testα=0.05).Results:The positive rate of Kiss-1 in nomal gallbladder tissues, para-tumor,tumor tissues and invasion tissues were(6/6)100%, (7/7)100%,(33/59)55.9%and(7/23)30.4%respectively,while the positive rate of KAI-1 were(6/6)100%,(6/7)85.7%,(20/59)33.9%,and (4/23)17.4%respectively,the tendency descended siginificantly.The positive rate of Kiss-1 and KAI-1 was down-regulated(p＜0.05) in tumor tissues,compared with non-tumor tissues.The positive rate of Kiss-1 and KAI-1 was down-regulated(p＜0.01) in invasion tissues,compared with para-tumor tissues.The positive rate of Kiss-1 in invasion tissues were significantly lower than in tumor tissues(p＜0.05);The positive rate of KAI-1 was down-regulated,but there was no statistical siginificance(p＞0.05).And to do with the data by Spearman rank correlation test,we find the positive rate of Kiss-1 and KAI-1 were all negatively correlated with the Nevin staging of gallbladder carcinoma(p＜0.01);And the positive rate of KAI-1 had a positive relationship with the differentiated degree of gallbladder carcinoma(p＜0.01).Moreover,a strong positive correlation was found between the positive expression of Kiss-1 and KAI-1 in gallbladder carcinoma(p＜0.01).Conclusions:It showed expression of Kiss-1 and KAI-1 in gallbladder carcinoma was down-regulated widespreadly,even absence(especially in advanced gallbladder carcinoma),and were negatively correlated with the malignant behavior of gallbladder carcinoma.It was indicated that low expression of Kiss-1 and/or KAI-1 was associated with the carcinogenesis and development of gallbladder carcinoma,especially with the metastasis and invasion,may be involved in regulation of this process.Kiss-1 and/or KAI-1 may be important markers of reflecting invasive and metastatic potential and prognosis in gallbladder carcinoma,and may be the target genes to inhibit metastasis of gallbladder carcinoma.Detection of the expression of Kiss-1 and/or KAI-1 may have important clinical value for finding early-stage and evaluating the prognosis of gallbladder carcinoma.