Expression And Significance Of Smac, Bcl-2 And Ki-67 In Pancreatic Cancer

Objective: Pancreatic Carcinoma is a digestive tract cancer with poor prognosis due to early local invasion or metabasis, radioresistivity and chemoresitivity. Smac is a proapoptotic protein resided in the intermembrane space of the mitochondria but is released into the cytosol during apoptosis, where it interacts with IAPs and disrupts their ability to bind caspases. Bcl-2 can protect the cell from damage. Ki-67 reflects cell proliferation ability. To analyze the role of these three genes in pancreatic carcinogenesis and to get clincal theraphy target for this tumor, we compare Smac, Bcl-2 and Ki-67 expression in this study.Methods: 30 pancreas carcinoma samples surgically removed between 2003-2007 years from the patients including 20 males and 10 females with average age of 59.33 in the Forth Hospital of Hebei Medical University. 11 samples in stageⅠ, 10 in stageⅡ, 4 in stageⅢand 5 in stageⅣwere used, 12 of 19 were dead with 3 years follow up. Tissue specimens were fixed in 10% buffered formalin and embedded in paraffin and performed on 4-μm sections for ten pieces, Smac, Bcl-2 and Ki-67 were stained, the expression levels were accessed in five areas of section and defined as four grades according to the percentage of positive cells. Briefly, the percentage of positive cells ranged at less than 5% as negative(-); 6% to 25% as weak positive(+); 26% to 50% as moderately positive(++); more than 50% as strong positive(+++).The slides were grades by two pathological physician with no backgroud with these samples, the average value were used.All statistical analyses were performed using SPSS 10.0 software. The difference of the expression was analyzed byχ2 test and Fisher's exact test. Spearman grading correlation analysis was used to analyze correlation. p<0.05 was defined significant.Result: 1 The Smac, Bcl-2 and Ki-67 expressional levels had no statistical difference refer to sex, age, and location, we considered all samples with different sex, age and location as same group.2 Features of the expression of Smac, Bcl-2 and Ki-67: Smac positive expression observed in pancreatic cancer shows a yellow cytolymp staining. Smac showed higher expression in higher-differented tissues and lower expression in lower- differented tissue. In the gradeⅠspecimens, 1 was strongly positive (+++), 1 was moderately positive (++); In the gradeⅡspecimens, 6 were strongly positive(+++), 10 were moderately positive(++),3 were weakly positive(+); In the gradeⅢspecimens, 1 was strongly positive (+++), 4 were moderately positive(++),3 were weakly positive(+). The Smac expressional levels according to different proliferated tissues was significantly different (p=0.045<0.05). Our data demontrated that Smac expression was positively correlated with differiented grades. Bcl-2 positive expression also observed in pancreatic cancer showed a yellow cytolymp staining. But Bcl-2 no statistical deffrence exist refered to differiented grades. Ki-67 positive expression observed in pancreatic cancer shows a brown nuclear staining. Ki-67 show lower expression in high-differented tissues and higher expression in lower-differented tissue. In the gradeⅠspecimens, 2 were moderately positive(++), 1 was negative(-). In the gradeⅡspecimens, 4 were strongly positive (+++), 7 were moderately positive(++),8 were weakly positive(+). In the gradeⅢspecimens, 6 were strongly positive(+++),2 were moderately positive(++). The difference of Ki-67 expression among differiented grades was significant (p=0.002<0.05). Our data demontrated that Ki-67 expression was negtively correlated with differiented grades.3 Comparison of Smac,Bcl-2 and Ki-67 with their clinical characteristicsNo statistical deffrence exist for Smac,Bcl-2 and Ki-67 expression refers to with clinical stages.The relationship of vessel or lymphonode invased with these three genes expression were compared subqently.Smac expression levels seemed not associated with invasion.Bcl-2 show higher expression in invasive tissues and lower expression in no invasive tissue. In invasive tissues, 11 was strongly positive(+++) to weakly positive(+), 1 was negative(-); In no invasive tissues, 8 were moderately positive(++) to weakly positive(+), 10 was negative(-). The difference of Bcl-2 expression between invision or no was significant (P=0.02 <0.05). Our data demontrated that Bcl-2 expression was positively correlated with invision.Ki-67 show higher expression in invasive tissues and lower expression in no invasive tissue. In invasive tissues, 11 were strong positive (+++) to moderately positive(++), 1 were weakly positive(+); In no invasive tissues, 10 were strong positive(+++) to moderately positive(++), 8 were weakly positive(+) to negative(-). The difference of Ki-67 expression between invision or no was significant (P=0.03<0.05). Our data demontrated that Ki-67 expression was positively correlated with invision.Conclusions: 1 Smac expression was positively correlated with differiented grades. Ki-67 show lower expression in high- differiented tissues and higher expression in lower-differiented tissue. The disturbance in the balance between cell apoptosis and proliferation may play an important role in the progression of pancreatic cancer.2 Bcl-2 expression was positively correlated with invision. Ki-67 expression was positively correlated with invision. They may play an important role in the progression of invision.