Relationship Between Expression of Ezrin Protein in Primary Carcinoma of Gallbladder and Positive Rates of CEA and CA19-9 in Serum_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WANG Fei , SUN Xuejun , ZHENG Jianbao , WANG Wei

Department of General Surgery, The First Affiliated Hospital of Medical College of Xi’an Jiaotong University, Xi’an 710061, ChinaCorresponding Author: SUN Xue-jun, E-mail: sunxy@mail.xjtu.edu.cn;

Corresponding author：

Keywords：

Primary carcinoma of gallbladder; Ezrin protein; CEA; CA19-9; Immunohistochemistry

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Objective 　To observe the expression of Ezrin protein in primary carcinoma of gallbladder tissue and the levels of CEA and CA19-9 in serum of patients with primary carcinoma of gallbladder, and to explore the relationship between the expressions of these measurements and clinicopathologic characteristics.
　　Methods 　Immunohistochemistry was applied to analyze the expression of Ezrin protein in primary carcinoma of gallbladder and chronic cholecystitis tissue. The levels of CEA and CA19-9 in serum and clinicopathologic characteristics of all including patients were detected with clinical measurement. All data were analyzed statistically.
　　Results 　①The positive rates of Ezrin protein in primary carcinoma of gallbladder and chronic cholecystitis tissue were 66.7% （40/60） and 30.8%（4/13）, respectively (χ2=5.57, P lt;0.05). ②There was no difference between the expression of Ezrin protein in primary carcinoma of gallbladder tissue and age or gender (P gt;0.05). However, difference was significant between the Ezrin expression and degree of difference, pNevin stages, pTNM stages, lymph node metastasis or distant metastasis (P lt;0.05). ③There were no differences between the positive rates of CEA and CA19-9 in primary carcinoma of gallbladder and age or gender (P gt;0.05). However, differences were significant between the positive rates of CEA and CA19-9 and pNevin stages, pTNM stages, degree of difference, lymph node metastasis or distant metastasis (P lt;0.05). ④There was some relationship between the expression of Ezrin protein and the positive rate of CEA (rs=0.213, P lt;0.05), but not with the positive rate of CA19-9 (rs=0.081, P gt;0.05).
　　Conclusions 　The high expression of Ezrin protein may promote the invasion and metastasis in primary carcinoma of gallbladder. It could be possible to decide the outcome of primary carcinoma of gallbladder through the combined analysis on the expression of Ezrin protein and the serum levels of CEA and CA19-9.

Citation： WANG Fei,SUN Xuejun,ZHENG Jianbao,WANG Wei. Relationship Between Expression of Ezrin Protein in Primary Carcinoma of Gallbladder and Positive Rates of CEA and CA19-9 in Serum. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2010, 17(4): 317-322. doi: Copy

1.	Niggli V, Rossy J. Ezrin/radixin/moesin: Versatile controllers of signaling molecules and of the cortical cytoskeleton [J]. Int J Biochem Cell Biol, 2008; 40(3): 344-349.
2.	Heiska L, Carpén O. Src phosphorylates ezrin at tyrosine 477 and induces a phosphospecific association between ezrin and a kelch-repeat protein family member [J]. J Biol Chem, 2005; 280(11): 10244-10252.
3.	Khanna C, Wan X, Bose S, et al. The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis [J]. Nat Med, 2004; 10(2): 182-186.
4.	Peng S, Fan S, Li X, et al. The expression of ezrin in NPC and its interaction with NGX6, a novel candidate suppressor [J]. Cancer Sci, 2007; 98(3): 341-349.
5.	Krishnan K, Bruce B， Hewitt S， et al. Ezrin mediates growth and survival in Ewing’s sarcoma through the AKT/mTOR, but not the MAPK, signaling pathway [J]. Clin Exp Metastasis， 2006; 23(3-4): 227-236.
6.	Mallikarjuna K, PushParaj V, Biswas J, et al. Expression of epidermal growth factor receptor, ezrin, hepatocyte growth factor, and c-Met in uveal melanoma: an immunohistochemical study [J]. Curr Eye Res， 2007; 32(3): 281-290.
7.	卢乐, 孙学军, 石景森. 胆囊癌临床分期研究的临床意义 [J]. 中华肝胆外科杂志, 2009; 15(1): 72-75.
8.	Sos＇nik K, Sos＇nik H. Some aspects of gallbladder carcinogenesis [J]. Wiad Lek， 2005； 58(11-12): 678-681.
9.	Hunter KW. Ezrin, a key component in tumor metastasis [J]. Trends Mol Med, 2004; 10(5): 201-204.
10.	Yu Y, Khan J, Khanna C, et al. Expression profiling identifies the cytoskeletal organizer ezrin and the developmental homeoprotein Six-1 as key metastatic regulators [J]. Nat Med, 2004; 10(2): 175-181.
11.	Akisawa N, Nishimori I, Iwamura T, et al. High levels of ezrin expressed by human pancreatic adenocarcinoma cell lines with high metastasis potential [J]. Biochem Biophys Res Commun, 1999; 258(2): 395-400.
12.	Bonilha VL, Rayborn ME, Saotome I, et al. Microvilli defects in retinas of ezrin knockout mice [J]. Exp Eye Res, 2006; 82(4): 720-729.
13.	Weng WH, Ahlén J, Astrm K, et al. Prognostic impact of immunohistochemical expression of ezrin in highly malignant soft tissue sarcomas [J]. Clin Cancer Res, 2005; 11(17): 6198-6204.
14.	Ilmonen S, Vaheri A, Asko-Seljavaara S, et al. Ezrin in primary cutaneous melanoma [J]. Mod Pathol, 2005; 18(4): 503-510.
15.	Valdman A, Fang X, Pang ST, et al. Ezrin expression in prostate cancer and benign prostatic tissue [J]. Eur Urol, 2005; 48(5): 852-857.
16.	Elliott BE, Meens JA, SenGupta SK, et al. The membrane cytoskeletal crosslinker Ezrin is required for metastasis of breast carcinoma cells [J]. Breast Cancer Res, 2005; 7(3): R365-R373.
17.	Shen ZY, Xu LY, Chen MH, et al. Upregulated expression of ezrin and invasive phenotype in malignantly transformed esophageal epithelial cells [J]. World J Gastroenterol, 2003; 9(6): 1182-1186.
18.	李琼, 吴明富, 宋安萍, 等. 浸润性乳腺导管癌组织中Ezrin和钙黏素E的表达与淋巴结转移的关系 [J]. 癌症, 2006; 25(3): 363-366.
19.	Moilanen J, Lassus H, Leminen A, et al. Ezrin immunoreactivity in relation to survival in serous ovarian carcinoma patients [J]. Gynecol Oncol, 2003; 90(2): 273-281.
20.	张俊会, 刘斌, 邢传平, 等. 胃癌组织ezrin表达的意义 [J]. 第四军医大学学报, 2007; 28(20): 1905-1907.
21.	Karmakar S, Das C. Modulation of ezrin and E-cadherin expression by IL-1β and TGF-β1 in human trophoblasts [J]. J Reprod Immunol, 2004; 64(1-2): 9-29.
22.	Fais S, De Milito A, Lozupone F. The role of FAS to ezrin association in FAS-mediated apoptosis [J]. Apoptosis, 2005; 10(5): 941-947.
23.	赵明, 季晓鹏, 王善菊, 等. 肿瘤标志物CA199与CEA联检对胰腺癌的诊断意义 [J]. 放射免疫学杂志, 2003; 16(6): 355.
24.	薛绮萍, 仇晓华, 王晓莲. 肿瘤标志物 TSGF及 CEA 对肿瘤的诊断价值探讨 [J]. 中国普外基础与临床杂志, 2001; 8(5): 331-332.
25.	刘洁琼，杨竹林，苗雄鹰. 胆囊良、恶性病变组织中CA19-9 和 CA125 的表达及其临床病理意义 [J]. 中国普外基础与临床杂志, 2008; 15(2): 92-95.

1. Niggli V, Rossy J. Ezrin/radixin/moesin: Versatile controllers of signaling molecules and of the cortical cytoskeleton [J]. Int J Biochem Cell Biol, 2008; 40(3): 344-349.
2. 　Heiska L, Carpén O. Src phosphorylates ezrin at tyrosine 477 and induces a phosphospecific association between ezrin and a kelch-repeat protein family member [J]. J Biol Chem, 2005; 280(11): 10244-10252.
3. 　Khanna C, Wan X, Bose S, et al. The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis [J]. Nat Med, 2004; 10(2): 182-186.
4. 　Peng S, Fan S, Li X, et al. The expression of ezrin in NPC and its interaction with NGX6, a novel candidate suppressor [J]. Cancer Sci, 2007; 98(3): 341-349.
5. 　Krishnan K, Bruce B， Hewitt S， et al. Ezrin mediates growth and survival in Ewing’s sarcoma through the AKT/mTOR, but not the MAPK, signaling pathway [J]. Clin Exp Metastasis， 2006; 23(3-4): 227-236.
6. 　Mallikarjuna K, PushParaj V, Biswas J, et al. Expression of epidermal growth factor receptor, ezrin, hepatocyte growth factor, and c-Met in uveal melanoma: an immunohistochemical study [J]. Curr Eye Res， 2007; 32(3): 281-290.
7. 　卢乐, 孙学军, 石景森. 胆囊癌临床分期研究的临床意义 [J]. 中华肝胆外科杂志, 2009; 15(1): 72-75.
8. 　Sos＇nik K, Sos＇nik H. Some aspects of gallbladder carcinogenesis [J]. Wiad Lek， 2005； 58(11-12): 678-681.
9. 　Hunter KW. Ezrin, a key component in tumor metastasis [J]. Trends Mol Med, 2004; 10(5): 201-204.
10. 　Yu Y, Khan J, Khanna C, et al. Expression profiling identifies the cytoskeletal organizer ezrin and the developmental homeoprotein Six-1 as key metastatic regulators [J]. Nat Med, 2004; 10(2): 175-181.
11. 　Akisawa N, Nishimori I, Iwamura T, et al. High levels of ezrin expressed by human pancreatic adenocarcinoma cell lines with high metastasis potential [J]. Biochem Biophys Res Commun, 1999; 258(2): 395-400.
12. 　Bonilha VL, Rayborn ME, Saotome I, et al. Microvilli defects in retinas of ezrin knockout mice [J]. Exp Eye Res, 2006; 82(4): 720-729.
13. 　Weng WH, Ahlén J, Astrm K, et al. Prognostic impact of immunohistochemical expression of ezrin in highly malignant soft tissue sarcomas [J]. Clin Cancer Res, 2005; 11(17): 6198-6204.
14. 　Ilmonen S, Vaheri A, Asko-Seljavaara S, et al. Ezrin in primary cutaneous melanoma [J]. Mod Pathol, 2005; 18(4): 503-510.
15. 　Valdman A, Fang X, Pang ST, et al. Ezrin expression in prostate cancer and benign prostatic tissue [J]. Eur Urol, 2005; 48(5): 852-857.
16. 　Elliott BE, Meens JA, SenGupta SK, et al. The membrane cytoskeletal crosslinker Ezrin is required for metastasis of breast carcinoma cells [J]. Breast Cancer Res, 2005; 7(3): R365-R373.
17. 　Shen ZY, Xu LY, Chen MH, et al. Upregulated expression of ezrin and invasive phenotype in malignantly transformed esophageal epithelial cells [J]. World J Gastroenterol, 2003; 9(6): 1182-1186.
18. 　李琼, 吴明富, 宋安萍, 等. 浸润性乳腺导管癌组织中Ezrin和钙黏素E的表达与淋巴结转移的关系 [J]. 癌症, 2006; 25(3): 363-366.
19. 　Moilanen J, Lassus H, Leminen A, et al. Ezrin immunoreactivity in relation to survival in serous ovarian carcinoma patients [J]. Gynecol Oncol, 2003; 90(2): 273-281.
20. 　张俊会, 刘斌, 邢传平, 等. 胃癌组织ezrin表达的意义 [J]. 第四军医大学学报, 2007; 28(20): 1905-1907.
21. 　Karmakar S, Das C. Modulation of ezrin and E-cadherin expression by IL-1β and TGF-β1 in human trophoblasts [J]. J Reprod Immunol, 2004; 64(1-2): 9-29.
22. 　Fais S, De Milito A, Lozupone F. The role of FAS to ezrin association in FAS-mediated apoptosis [J]. Apoptosis, 2005; 10(5): 941-947.
23. 　赵明, 季晓鹏, 王善菊, 等. 肿瘤标志物CA199与CEA联检对胰腺癌的诊断意义 [J]. 放射免疫学杂志, 2003; 16(6): 355.
24. 　薛绮萍, 仇晓华, 王晓莲. 肿瘤标志物 TSGF及 CEA 对肿瘤的诊断价值探讨 [J]. 中国普外基础与临床杂志, 2001; 8(5): 331-332.
25. 　刘洁琼，杨竹林，苗雄鹰. 胆囊良、恶性病变组织中CA19-9 和 CA125 的表达及其临床病理意义 [J]. 中国普外基础与临床杂志, 2008; 15(2): 92-95.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Relationship Between Expression of Ezrin Protein in Primary Carcinoma of Gallbladder and Positive Rates of CEA and CA19-9 in Serum

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