• 1.上海交通大學(xué)醫(yī)學(xué)院附屬第三人民醫(yī)院普外科(上海 201900);;
  • 2.上海交通大學(xué)醫(yī)學(xué)院附屬第三人民醫(yī)院病理科(上海 201900);

目的探討神經(jīng)細(xì)胞黏附分子——接觸蛋白-1(CNTN-1)、血管內(nèi)皮生長(zhǎng)因子-C(VEGF-C)及其受體VEGFR-3(Flt-4)在原發(fā)性胃癌組織中的表達(dá)，并分析三者的相關(guān)性及其與臨床病理特征的關(guān)系。方法選取68例原發(fā)性胃癌患者腫瘤原發(fā)灶和正常胃黏膜組織標(biāo)本，行免疫組化染色檢測(cè)VEGF-C、VEGFR-3和CNTN-1蛋白表達(dá)，測(cè)定VEGFR-3陽(yáng)性淋巴管密度(FVD)和D2-40陽(yáng)性淋巴管密度(LVD)。結(jié)果胃癌組織中VEGF-C、VEGFR-3和CNTN-1蛋白表達(dá)陽(yáng)性率分別為57.4%(39/68)、60.3%(41/68)和55.9%(38/68)，顯著高于正常胃黏膜組織〔20.6%(14/68)、23.5%(16/68)、16.2%(11/68)〕，P=0.000。在TNM分期較晚、發(fā)生淋巴管浸潤(rùn)和淋巴結(jié)轉(zhuǎn)移的患者其腫瘤組織中三者的表達(dá)陽(yáng)性率均較高(P lt;0.05)。CNTN-1蛋白表達(dá)與VEGF-C(r=0.372，P=0.002)及VEGFR-3蛋白(r=0.308，P=0.011)表達(dá)之間呈正相關(guān)。68例患者腫瘤組織中FVD為(10.41±9.38)個(gè)/HP，明顯低于其LVD〔(18.19±7.44)個(gè)/HP〕，P=0.000。在TNM分期較晚、有淋巴管浸潤(rùn)和淋巴結(jié)轉(zhuǎn)移的患者腫瘤組織中，F(xiàn)VD與LVD均較高(P lt;0.05)。VEGF-C和CNTN-1蛋白表達(dá)陽(yáng)性者FVD明顯高于表達(dá)陰性者(P=0.029和P=0.003); LVD與CNTN1(P=0.727)、VEGF-C(P=0.173)和VEGFR-3蛋白(P=0.924)表達(dá)均無(wú)關(guān)。 VEGF-C、VEGFR-3及CNTN-1蛋白表達(dá)陽(yáng)性患者術(shù)后生存率分別較表達(dá)陰性患者低(P lt;0.05)。結(jié)論CNTN-1蛋白在胃癌組織中高表達(dá)，與VEGF-C和VEGFR-3蛋白表達(dá)相關(guān)，聯(lián)合檢測(cè)對(duì)判斷胃癌侵襲性和預(yù)后有重要參考價(jià)值。 VEGF-C可能通過(guò)CNTN-1通路介導(dǎo)淋巴管生成，從而促進(jìn)胃癌的淋巴浸潤(rùn)。

引用本文： 吳生華,俞繼衛(wèi),鄭林海,吳巨鋼,倪曉春,李曉強(qiáng),杜光燁,姜波健. CNTN-1、VEGF-C和VEGFR-3在胃癌組織中的表達(dá)及其臨床意義. 中國(guó)普外基礎(chǔ)與臨床雜志, 2011, 18(2): 142-148. doi: 復(fù)制

1. Albuquerque RJ, Hayashi T, Cho WG, et al. Alternatively spliced vascular endothelial growth factor receptor2 is an essential endogenous inhibitor of lymphatic vessel growth [J]. Nat Med, 2009, 15(9): 10231030.
2. Lohela M, Bry M, Tammela T, et al. VEGFs and receptors involved in angiogenesis versus lymphangiogenesis [J]. Curr Opin Cell Biol, 2009, 21(2): 154165.
3. Matsumura S, Oue N, Mitani Y, et al. DNA demethylation of vascular endothelial growth factorC is associated with gene expression and its possible involvement of lymphangiogenesis in gastric cancer [J]. Int J Cancer, 2007, 120(8): 16891695.
4. Mkinen T, Norrmén C, Petrova TV. Molecular mechanisms of lymphatic vascular development [J]. Cell Mol Life Sci, 2007, 64(15): 19151929.
5. Morita H, Ishikawa Y, AkishimaFukasawa Y, et al. Histopathological predictor for regional lymph node metastasis in gastric cancer [J]. Virchows Arch, 2009, 454(2): 143151.
6. Su JL, Yang PC, Shih JY, et al. The VEGFC/Flt4 axis promotes invasion and metastasis of cancer cells [J]. Cancer Cell, 2006, 9(3): 209223.
7. Su JL, Yang CY, Shih JY, et al. Knockdown of contactin1 expression suppresses invasion and metastasis of lung adenocarcinoma [J]. Cancer Res, 2006, 66(5): 25532561.
8. Yonemura Y, Endou Y, Tabachi K, et al. Evaluation of lymphatic invasion in primary gastric cancer by a new monoclonal antibody, D240 [J]. Hum Pathol, 2006, 37(9): 11931199.
9. Kodama M, Kitadai Y, Tanaka M, et al. Vascular endothelial growth factor C stimulates progression of human gastric cancer via both autocrine and paracrine mechanisms [J]. Clin Cancer Res, 2008, 14(22): 72057214.
10. Sobin LH, Fleming ID. TNM Classification of Malignant Tumors, fifth edition (1997). Union Internationale Contre le Cancer and the American Joint Committee on Cancer [J]. Cancer, 1997, 80(9): 18031804.
11. Weidner N, Semple JP, Welch WR, et al. Tumor angiogenesis and metastasis-correlation in invasive breast carcinoma [J]. N Engl J Med, 1991, 324(1): 18.
12. Skobe M, Dana R. Blocking the path of lymphatic vessels [J]. Nat Med, 2009, 15(9): 993994.
13. Da MX, Wu XT, Wang J, et al. Expression of cyclooxygenase2 and vascular endothelial growth factorC correlates with lymphangiogenesis and lymphatic invasion in human gastric cancer [J]. Arch Med Res, 2008, 39(1): 9299.
14. 吳立剛, 劉奇?zhèn)? 胡志強(qiáng). MMP2和VEGFC在甲狀腺乳頭狀癌中的表達(dá)及臨床意義 [J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2009, 16(11): 906910.
15. 黃桂林, 侯吉學(xué), 吳毅平. 乳腺癌患者血清VEGFC水平與癌組織CerbB2蛋白的表達(dá)及臨床意義 [J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2009, 16(7): 514517.
16. Wang XL, Fang JP, Tang RY, et al. Different significance between intratumoral and peritumoral lymphatic vessel density in gastric cancer: a retrospective study of 123 cases [J]. BMC Cancer, 2010, 10: 299.
17. Vondenhoff MF, Greuter M, Goverse G, et al. LTbetaR signaling induces cytokine expression and upregulates lymphangiogenic factors in lymph node anlagen [J]. J Immunol, 2009, 182(9): 54395445.
18. He M, Cheng Y, Li W, et al. Vascular endothelial growth factor C promotes cervical cancer metastasis via upregulation and activation of RhoA/ROCK2/moesin cascade [J]. BMC Cancer, 2010, 10: 170.
19. Sung JY, Lee S, Kim YW, et al. Vascular endothelial growth factor receptor3 is a favorable prognostic factor in advanced gastric carcinoma [J]. Oncol Rep, 2008, 19(4): 939944.
20. Revest J M, FaivreSarrailh C, Maeda N, et al. The interaction between F3 immunoglobulin domains and protein tyrosine phosphatases zeta/beta triggers bidirectional signalling between neurons and glial cells [J]. Eur J Neurosci, 1999, 11(4): 11341147.
21. Sakurai T, Lustig M, Nativ M, et al. Induction of neurite outgrowth through contactin and NrCAM by extracellular regions of glial receptor tyrosine phosphatase beta [J]. J Cell Biol, 1997, 136(4): 907918.
22. Zeng L, D’Alessandri L, Kalousek MB, et al. Protein tyrosine phosphatase alpha (PTPalpha) and contactin form a novel neuronal receptor complex linked to the intracellular tyrosine kinase fyn [J]. J Cell Biol, 1999, 147(4): 707714.
23. Huang J, Asawa T, Takato T, et al. Cooperative roles of Fyn and cortactin in cell migration of metastatic murine melanoma [J]. J Biol Chem, 2003, 278(48): 4836748376.
  1. 1. Albuquerque RJ, Hayashi T, Cho WG, et al. Alternatively spliced vascular endothelial growth factor receptor2 is an essential endogenous inhibitor of lymphatic vessel growth [J]. Nat Med, 2009, 15(9): 10231030.
  2. 2. Lohela M, Bry M, Tammela T, et al. VEGFs and receptors involved in angiogenesis versus lymphangiogenesis [J]. Curr Opin Cell Biol, 2009, 21(2): 154165.
  3. 3. Matsumura S, Oue N, Mitani Y, et al. DNA demethylation of vascular endothelial growth factorC is associated with gene expression and its possible involvement of lymphangiogenesis in gastric cancer [J]. Int J Cancer, 2007, 120(8): 16891695.
  4. 4. Mkinen T, Norrmén C, Petrova TV. Molecular mechanisms of lymphatic vascular development [J]. Cell Mol Life Sci, 2007, 64(15): 19151929.
  5. 5. Morita H, Ishikawa Y, AkishimaFukasawa Y, et al. Histopathological predictor for regional lymph node metastasis in gastric cancer [J]. Virchows Arch, 2009, 454(2): 143151.
  6. 6. Su JL, Yang PC, Shih JY, et al. The VEGFC/Flt4 axis promotes invasion and metastasis of cancer cells [J]. Cancer Cell, 2006, 9(3): 209223.
  7. 7. Su JL, Yang CY, Shih JY, et al. Knockdown of contactin1 expression suppresses invasion and metastasis of lung adenocarcinoma [J]. Cancer Res, 2006, 66(5): 25532561.
  8. 8. Yonemura Y, Endou Y, Tabachi K, et al. Evaluation of lymphatic invasion in primary gastric cancer by a new monoclonal antibody, D240 [J]. Hum Pathol, 2006, 37(9): 11931199.
  9. 9. Kodama M, Kitadai Y, Tanaka M, et al. Vascular endothelial growth factor C stimulates progression of human gastric cancer via both autocrine and paracrine mechanisms [J]. Clin Cancer Res, 2008, 14(22): 72057214.
  10. 10. Sobin LH, Fleming ID. TNM Classification of Malignant Tumors, fifth edition (1997). Union Internationale Contre le Cancer and the American Joint Committee on Cancer [J]. Cancer, 1997, 80(9): 18031804.
  11. 11. Weidner N, Semple JP, Welch WR, et al. Tumor angiogenesis and metastasis-correlation in invasive breast carcinoma [J]. N Engl J Med, 1991, 324(1): 18.
  12. 12. Skobe M, Dana R. Blocking the path of lymphatic vessels [J]. Nat Med, 2009, 15(9): 993994.
  13. 13. Da MX, Wu XT, Wang J, et al. Expression of cyclooxygenase2 and vascular endothelial growth factorC correlates with lymphangiogenesis and lymphatic invasion in human gastric cancer [J]. Arch Med Res, 2008, 39(1): 9299.
  14. 14. 吳立剛, 劉奇?zhèn)? 胡志強(qiáng). MMP2和VEGFC在甲狀腺乳頭狀癌中的表達(dá)及臨床意義 [J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2009, 16(11): 906910.
  15. 15. 黃桂林, 侯吉學(xué), 吳毅平. 乳腺癌患者血清VEGFC水平與癌組織CerbB2蛋白的表達(dá)及臨床意義 [J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2009, 16(7): 514517.
  16. 16. Wang XL, Fang JP, Tang RY, et al. Different significance between intratumoral and peritumoral lymphatic vessel density in gastric cancer: a retrospective study of 123 cases [J]. BMC Cancer, 2010, 10: 299.
  17. 17. Vondenhoff MF, Greuter M, Goverse G, et al. LTbetaR signaling induces cytokine expression and upregulates lymphangiogenic factors in lymph node anlagen [J]. J Immunol, 2009, 182(9): 54395445.
  18. 18. He M, Cheng Y, Li W, et al. Vascular endothelial growth factor C promotes cervical cancer metastasis via upregulation and activation of RhoA/ROCK2/moesin cascade [J]. BMC Cancer, 2010, 10: 170.
  19. 19. Sung JY, Lee S, Kim YW, et al. Vascular endothelial growth factor receptor3 is a favorable prognostic factor in advanced gastric carcinoma [J]. Oncol Rep, 2008, 19(4): 939944.
  20. 20. Revest J M, FaivreSarrailh C, Maeda N, et al. The interaction between F3 immunoglobulin domains and protein tyrosine phosphatases zeta/beta triggers bidirectional signalling between neurons and glial cells [J]. Eur J Neurosci, 1999, 11(4): 11341147.
  21. 21. Sakurai T, Lustig M, Nativ M, et al. Induction of neurite outgrowth through contactin and NrCAM by extracellular regions of glial receptor tyrosine phosphatase beta [J]. J Cell Biol, 1997, 136(4): 907918.
  22. 22. Zeng L, D’Alessandri L, Kalousek MB, et al. Protein tyrosine phosphatase alpha (PTPalpha) and contactin form a novel neuronal receptor complex linked to the intracellular tyrosine kinase fyn [J]. J Cell Biol, 1999, 147(4): 707714.
  23. 23. Huang J, Asawa T, Takato T, et al. Cooperative roles of Fyn and cortactin in cell migration of metastatic murine melanoma [J]. J Biol Chem, 2003, 278(48): 4836748376.