Expressions and Significances of NF-κB and EGFR in Hepatolithiasis Associated with Intrahepatic Cholangiocarcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

HUANG Fen ¹ , CHEN Rufu ¹ , ZHOU Quanbo ¹ , LI Haigang. ²

1.Department of Hepatobiliary Surgery, The 2nd Affiliated Hospital, Sun Yat-sen University, Guangzhou 510120, China;;
2.Department of Pathology, The 2nd Affiliated Hospital, Sun Yat-sen University, Guangzhou 510120, China;

Corresponding author：

Keywords：

Nuclear factor kappa B; Epidermal growth factor receptor; Cholelithiasis; Cholangiocarcinoma; Intrahepatic

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Objective To investigate the roles of NF-κB and EGFR in hepatolithiasis associated with intrahepatic cholangiocarcinoma. Methods Ninety cases of liver tissue specimens from hepatectomies performed in the 2nd Affiliated Hospital of Sun Yat-sen University between August 1989 and June 2009 were enrolled in the study. Among them, 33 cases of hepatolithiasis associated with intrahepatic cholangiocarcinoma were considered as observing group, 32 cases of hepatolithiasis as control group, and 25 cases of normal bile duct tissues as normal control group. The SP method of immunohistochemical staining was applied to detect the expressions of NF-κB and EGFR in intrahepatic biliary ducts epithelial cells, and their relations with clinicopathologic factors and the accumulated survival rate of hepatolithiasis associated with intrahepatic cholangiocarcinoma were analyzed. Results Expression rates of NF-κB and EGFR were gradually raised from normal control group, control group to observing group (P lt;0.01). Expression of EGFR in tumor patients was related to histopathologic differentiation grading and the depth of tumor invasion (P lt;0.05), but not to gender, age, or lymph node metastasis (P gt;0.05)； there were no significant relationships between the expression of NF-κB and factors described above (P gt;0.05). The survival rate of patients with tumor expressed EGFR was significantly lower than that of patients with tumor non-expressed EGFR (P lt;0.01). Conclusions NF-κB expression is in the early stage during intrahepatic cholangiocarcinoma genesis. NF-κB and EGFR play cooperating roles during hepatolithiasis carcinogenesis process. Over expression of EGFR is related with poor differentiation and prognosis of tumor.

Citation： HUANG Fen,CHEN Rufu,ZHOU Quanbo,LI Haigang.. Expressions and Significances of NF-κB and EGFR in Hepatolithiasis Associated with Intrahepatic Cholangiocarcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2010, 17(11): 1158-1163. doi: Copy

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1. 虞积耀，崔全才主译. 消化系统肿瘤病理学和遗传学分册·世界卫生组织肿瘤分类及诊断标准系列图书 [M]. 北京: 人民卫生出版社; 2006: 210-217.
2. Gores GJ. Cholangiocarcinoma: current concepts and insights [J]. Hepatology, 2003; 37(5): 961-969.
3. Malhi H, Gores GJ. Cholangiocarcinoma: modern advances in understanding a deadly old disease [J]. J Hepatol, 2006; 45(6): 856-867.
4. Sugawara H, Yasoshima M, Katayanagi K, et al. Relationship between interleukin-6 and proliferation and differentiation in cholangiocarcinoma. [J]. Histopathology, 1998; 33(2): 145-153.
5. Kobayashi S, Werneburg NW, Bronk SF, et al. Interleukin-6 contributes to Mcl-1 up-regulation and TRAIL resistance via an Akt-signaling pathway in cholangiocarcinoma cells [J]. Gastroenterology, 2005; 128(7): 2054-2065.
6. Isomoto H, Mott JL, Kobayashi S, et al. Sustained IL-6/STAT-3 signaling in cholangiocarcinoma cells due to SOCS-3 epigenetic silencing [J]. Gastroenterology, 2007; 132(1): 384-396.
7. Yoon JH, Werneburg NW, Higuchi H, et al. Bile acids inhibit Mcl-1 protein turnover via an epidermal growth factor receptor/Raf-1-dependent mechanism [J]. Cancer Res, 2002; 62(22): 6500-6505.
8. Werneburg NW, Yoon JH, Higuchi H, et al. Bile acids activate EGF receptor via a TGF-alpha-dependent mechanism in human cholangiocyte cell lines [J]. Am J Physiol Gastrointest Liver Physiol, 2003; 285(1): G31-G36.
9. Yamagiwa Y, Meng F, Patel T. Interleukin-6 decreases senescence and increases telomerase activity in malignant human cholangiocytes [J]. Life Sci, 2006; 78(21): 2494-2502.
10. Andrzejewska A, Jurkowska G. Nitric oxide protects the ultrastructure of pancreatic acinar cells in the course of caerulein-induced acute pancreatitis [J]. Int J Exp Pathol, 1999; 80(6): 317-324.
11. Nishino T, Watanabe S, Oyama H, et al. An endothelial nitric oxide synthase inhibitor aggravates CDL-induced acute pancreatitis in rats [J]. Pancreas, 1999; 19(4): 390-400.
12. 陈汝福, 李志花, 陈积圣. 丙型肝炎核心蛋白活化肝门部胆管癌细胞中NF-κB介导的信号转导途径 [J]. 中华实验外科杂志, 2003； 20(3): 227-228.
13. 张浩，李昱骥，周建平，等. 表皮生长因子促进胰腺癌细胞侵袭和转移的实验研究 [J]. 中国普外基础与临床杂志， 2008; 15(3): 180-184.
14. 刘宇，张浩，杨野，等. 表皮生长因子介导的NF-κB促进胰腺癌细胞MMP-9表达及侵袭的实验研究 [J]. 中国普外基础与临床杂志, 2009; 16(8): 603-608.
15. 王文举, 李鸿钧, 孙茂盛. NF-κB与持久炎症及肿瘤发生关系 [J]. 生命的化学, 2007； 27(3): 197-199.
16. Denning MF, Dlugosz AA, Cheng C, et al. Cross-talk between epidermal growth factor receptor and protein kinase C during calcium-induced differentiation of keratinocytes [J]. Exp Dermatol, 2000; 9(3): 192-199.
17. 杨焱，李相成，王学浩，等. 肝素结合的类表皮生长因子促进大鼠减体积肝移植术后移植肝细胞的再生 [J]. 中国普外基础与临床杂志， 2008； 15(3)： 155-158.
18. 付建华，赵曼，胡国强，等. EGFR和E-cadherin与肿瘤的发生发展及其调控机制的研究进展 [J]. 实用癌症杂志， 2008; 23（1）： 107-109.
19. Molinari F, Martin V, Saletti P, et al. Differing deregulation of EGFR and downstream proteins in primary colorectal cancer and related metastatic sites may be clinically relevant [J]. Br J Cancer, 2009; 100(7): 1087-1094.
20. Ciardiello F, Tortora G. EGFR antagonists in cancer treatment [J]. N Engl J Med, 2008; 358(11): 1160-1174.
21. 郁宝铭. 结直肠癌分子靶向治疗药物研究现状 [J]. 世界华人消化杂志， 2008； 16(33): 3705-3712.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expressions and Significances of NF-κB and EGFR in Hepatolithiasis Associated with Intrahepatic Cholangiocarcinoma

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