The Expression Of Survivin,Livin And VEGF In Cholangiocarcinoma

Objective: Cholangiocarcinoma is one of the most common malignant tumors in bile duct. Recently, the morbidity of Cholangiocarcinoma has an increasing tendency in malignant tumors in our country. This experiment is to study the expression of Survivin, Livin and VEGF protein in Cholangiocarcinoma, to investigate the correlation of the expression of Survivin, Livin and VEGF protein with clinical pathological characteristics in Cholangiocarcinoma, also to investigate the correlation between Survivin, Livin and VEGF. Then it shows the relationships of Survivin, Livin and VEGF with carcinogenesis, progression and prognosis of Cholangiocarcinoma. Therefore the result may provide new theoretical basis for the treatment of Cholangiocarcinoma.Method: Extrahepatic cholangiocarcinoma specimens with full clinicopathological data were selected and confirmed by the postoperative pathologic diagnosis. There were 19 men and 11 women, with mean age of 56 years old. Histological differentiation: high, 12 cases; moderate, 10 cases; low, 8 cases. The clinical stage was divided according to the standard of UICC (1997): stages I and II, 16cases; stage III and IV, 14 cases. There were 22 cases with local lymph node metastasis and 8 cases without. Twenty cases of benign lesion of EHBD ( extrahepatic bile duct) were studied as control. Specimens were fixed with formalin, embedded with paraffin and cut into 4μm paraffin slices, and then immunohistochemical staining for Survivin Livin and Smac were performed. All data were tested by x2-test or Spearman rank correlation test (P<0.05 was considered statistical significance).Results:1 The expression of Survivin protein in cholangiocarcinoma and benign lesion of EHBD: The Survivin expression rate in cholangiocarcinoma was 63.33% (19/30), but there was 2 positive cases in benign lesion of EHBD (2/20). The difference was signficant(χ2=14.01, P<0.05). (Table 1) In cholangiocarcinoma, Survivin total positive rate was 56.25% (9/16) in stages I and II, and 71.43% (10/14) in stage III and IV respectively. There was no statistical significance between them (P>0.05). The expression rate of Survivin in high and middle-low histological differentiation groups were 50.00% (6/12) and 72.22% (13/18), respectively. Also there was no statistical significance between them (P>0.05). Survivin positive rate was 81.82% (18/22) in patients with lymph node metastasis and 12.50% (1/8) in those without lymph node metastasis. There was significant association between expression of Survivin and metastasis (P <0.05). (Table 4).2 The expression of Livin protein in cholangiocarcinoma and benign lesion of EHBD: The Livin expression rate in cholangiocarcinoma was 56.67% (17/30), but there was no expression of Livin in benign lesion of EHBD (0/20). The difference was signficant(χ2=17.17, P<0.05). (Table 2) In cholangiocarcinoma, Livin total positive rate was 62.50% (10/16) in stages I and II, and 50.00% (7/14) in stage III and IV, respectively. There was no statistical significance between them (P>0.05). The expression rate of Livin in high and middle-low histological differentiation groups were 58.33% (7/12) and 55.56% (10/18), respectively. Also there was no statistical significance between them (P>0.05). Livin positive rate was 72.73% (16/22) in patients with lymph node metastasis and 12.50% (1/8) in those without lymph node metastasis. There was significant association between expression of Livin and metastasis (P <0.05) (Table 5).3 The expression of VEGF protein in cholangiocarcinoma and benign lesion of EHBD: The VEGF expression rate in cholangiocarcinoma was 70.00% (21/30), however there was 1 positive cases in benign lesion of EHBD (1/20). The difference was signficant(χ2=20.58, P<0.05). (Table 3) In cholangiocarcinoma, VEGF total positive rate was 75.00% (12/16) in stages I and II, and 64.29% (9/14) in stage III and IV, respectively. There was no statistical significance between them (P>0.05). The expression rate of VEGF in high and middle-low histological differentiation groups were 75.00% (9/12) and 66.67% (12/18), respectively. Also there was no statistical significance between them (P>0.05). VEGF positive rate was 95.45% (21/22) in patients with lymph node metastasis , but there was no expression of VEGF in those without lymph node metastasis. There was significant association between expression of VEGF and metastasis (P <0.05). (Table 6).4 Correlations of the expression of Survivin,Livin and VEGF in cholangiocarcinoma:In these study we found that There was a positive correlation between the expression of Survivin and VEGF in cholangiocarcinoma (rs=0.41, P<0.05). (Table 8) Also there was a positive correlation between the expression of Livin and VEGF in cholangiocarcinoma (rs=0.46, P<0.05). (Table 9) However There was on correlation between the expression of Survivin and Livin in cholangiocarcinoma (P>0.05). (Table 7)Conclusion: In this study we found that the expression rate of Survivin,Livin and VEGF in cholangiocarcinoma and benign lesion of EHBD were significantly different. The expression of Survivin,Livin and VEGF in cholangiocarcinoma were higher than that in benign lesion of EHBD, suggesting that Survivin,Livin and VEGF may play an important role in the occurrence and development of cholangiocarcinoma. Additionally, the expression of Survivin,Livin and VEGF had no significant correlation with TNM stage and histological differentiated degree, but had great correlation with lymph node metastasis, suggesting that Survivin,Livin and VEGF may predict prognosis. Moreover, we also found that There was on correlation between the expression of Survivin and Livin in cholangiocarcinoma, indicating that there were some different mechanisms in the process of apoptosis. But there was a positive correlation between the expression of Survivin and VEGF in cholangiocarcinoma, besides the expression of Livin and VEGF, indicating that they were closely associated with the angiogenesis of cholangiocarcinoma.