• 西安交通大學(xué)醫(yī)學(xué)院第一附屬醫(yī)院普外科（西安 710061）;

【摘要】　目的 　探討原發(fā)性膽囊癌組織中Ezrin蛋白表達(dá)和膽囊癌患者血清中CEA及CA19-9檢測陽性率與其臨床病理因素之間的關(guān)系及其意義； 并分析膽囊癌組織中Ezrin蛋白表達(dá)與血清CEA和CA19-9陽性率之間的相關(guān)性。
　　方法 　應(yīng)用免疫組織化學(xué)方法檢測60例膽囊癌組織和13例慢性膽囊炎組織中Ezrin蛋白的表達(dá)； 收集所有研究對象的各項(xiàng)臨床病理指標(biāo)和CEA及CA19-9檢測值，并進(jìn)行統(tǒng)計學(xué)分析。
　　結(jié)果 　①Ezrin蛋白在原發(fā)性膽囊癌和慢性膽囊炎組織中的表達(dá)陽性率分別為66.7%(40/60)和30.8%(4/13)，前者明顯高于后者(χ2 =5.57，P lt;0.05)。②Ezrin蛋白在原發(fā)性膽囊癌組織中的表達(dá)與患者的年齡、性別無關(guān)(P gt;0.05)，與組織分化程度、淋巴結(jié)或遠(yuǎn)處轉(zhuǎn)移、pNevin分期及pTNM分期均有關(guān)(P lt;0.05)。③血清CEA及CA19-9檢測陽性率與患者性別和年齡無關(guān)(P gt;0.05)，分別與pNevin分期、pTNM分期、組織分化程度及淋巴結(jié)或遠(yuǎn)處轉(zhuǎn)移有關(guān)(P lt;0.05)。④膽囊癌組織中Ezrin蛋白表達(dá)與血清CEA檢測陽性率之間存在一定的相關(guān)性(rs=0.213，P lt;0.05)，與CA19-9檢測陽性率之間無明確相關(guān)性(rs=0.081，P gt;0.05)。
　　結(jié)論 　Ezrin蛋白在原發(fā)性膽囊癌組織中高表達(dá)可能促進(jìn)了腫瘤的發(fā)展和轉(zhuǎn)移； 檢測膽囊癌組織中Ezrin蛋白的表達(dá)及血清中CEA和CA19-9水平，將有助于對膽囊癌的發(fā)生、發(fā)展、轉(zhuǎn)移和預(yù)后作出綜合判斷。

引用本文： 王菲,孫學(xué)軍,鄭見寶,王煒. Ezrin蛋白在膽囊癌組織中的表達(dá)及其與血清CEA及CA19-9陽性率的關(guān)系. 中國普外基礎(chǔ)與臨床雜志, 2010, 17(4): 317-322. doi: 復(fù)制

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. 　盧樂, 孫學(xué)軍, 石景森. 膽囊癌臨床分期研究的臨床意義 [J]. 中華肝膽外科雜志, 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. 　李瓊, 吳明富, 宋安萍, 等. 浸潤性乳腺導(dǎo)管癌組織中Ezrin和鈣黏素E的表達(dá)與淋巴結(jié)轉(zhuǎn)移的關(guān)系 [J]. 癌癥, 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. 　張俊會, 劉斌, 邢傳平, 等. 胃癌組織ezrin表達(dá)的意義 [J]. 第四軍醫(yī)大學(xué)學(xué)報, 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. 　趙明, 季曉鵬, 王善菊, 等. 腫瘤標(biāo)志物CA199與CEA聯(lián)檢對胰腺癌的診斷意義 [J]. 放射免疫學(xué)雜志, 2003; 16(6): 355.
24. 　薛綺萍, 仇曉華, 王曉蓮. 腫瘤標(biāo)志物 TSGF及 CEA 對腫瘤的診斷價值探討 [J]. 中國普外基礎(chǔ)與臨床雜志, 2001; 8(5): 331-332.
25. 　劉潔瓊， 楊竹林， 苗雄鷹. 膽囊良、惡性病變組織中CA19-9 和 CA125 的表達(dá)及其臨床病理意義 [J]. 中國普外基礎(chǔ)與臨床雜志, 2008; 15(2): 92-95.
  1. 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. 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. 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. 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. 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. 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. 7. 　盧樂, 孫學(xué)軍, 石景森. 膽囊癌臨床分期研究的臨床意義 [J]. 中華肝膽外科雜志, 2009; 15(1): 72-75.
  8. 8. 　Sos＇nik K, Sos＇nik H. Some aspects of gallbladder carcinogenesis [J]. Wiad Lek， 2005； 58(11-12): 678-681.
  9. 9. 　Hunter KW. Ezrin, a key component in tumor metastasis [J]. Trends Mol Med, 2004; 10(5): 201-204.
  10. 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. 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. 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. 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. 14. 　Ilmonen S, Vaheri A, Asko-Seljavaara S, et al. Ezrin in primary cutaneous melanoma [J]. Mod Pathol, 2005; 18(4): 503-510.
  15. 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. 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. 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. 18. 　李瓊, 吳明富, 宋安萍, 等. 浸潤性乳腺導(dǎo)管癌組織中Ezrin和鈣黏素E的表達(dá)與淋巴結(jié)轉(zhuǎn)移的關(guān)系 [J]. 癌癥, 2006; 25(3): 363-366.
  19. 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. 20. 　張俊會, 劉斌, 邢傳平, 等. 胃癌組織ezrin表達(dá)的意義 [J]. 第四軍醫(yī)大學(xué)學(xué)報, 2007; 28(20): 1905-1907.
  21. 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. 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. 23. 　趙明, 季曉鵬, 王善菊, 等. 腫瘤標(biāo)志物CA199與CEA聯(lián)檢對胰腺癌的診斷意義 [J]. 放射免疫學(xué)雜志, 2003; 16(6): 355.
  24. 24. 　薛綺萍, 仇曉華, 王曉蓮. 腫瘤標(biāo)志物 TSGF及 CEA 對腫瘤的診斷價值探討 [J]. 中國普外基礎(chǔ)與臨床雜志, 2001; 8(5): 331-332.
  25. 25. 　劉潔瓊， 楊竹林， 苗雄鷹. 膽囊良、惡性病變組織中CA19-9 和 CA125 的表達(dá)及其臨床病理意義 [J]. 中國普外基礎(chǔ)與臨床雜志, 2008; 15(2): 92-95.