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VEGF-C和CD44v6在原发性肝细胞癌中的表达及临床意义
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摘要
目的:探讨血管内皮细胞生长因子-C(VEGF-C)和CD44v6在原发性肝细胞癌中的表达及其与肝癌部分生物学行为的关系。
     方法:采用常规SP免疫组织化学染色检测33例原发性肝细胞癌患者标本中VEGF-C和CD44v6的表达,并以21例肝硬化患者、16例肝外伤或肝囊肿等患者标本作为对照,分析其表达水平与肝癌部分生物学行为,如组织学分级、肿瘤直径、是否伴有肝内外转移、合并肝硬化情况、甲胎蛋白(AFP)、有无HBV感染等指标间的关系。
     结果:①VEGF-C定位于肝癌细胞细胞质,阳性表达率为78.8%(26/33);在转移组的表达率为94.1%(16/17),明显高于无转移组62.5%(10/16),P<0.05;癌组织中的表达明显高于癌旁组织36.4%(12/33),P<0.05;非肝癌手术后的肝脏组织中几乎不表达;而在组织学分级、肿瘤大小、是否合并肝硬化、AFP表达、有无HBV感染间未见明显差异。②CD44v6主要定位于肝癌细胞的胞膜及胞质,阳性表达率为72.7%(24/33);在发生转移的肝癌组织中CD44v6阳性表达率为94.1%(16/17),高于无转移的肝癌组织中CD44v6阳性表达率50.0%(8/16),P<0.05;癌组织中的表达明显高于癌旁组织33.3%(11/33),P<0.05;非肝癌手术后的肝脏组织中CD44v6几乎不表达或仅在少量淋巴细胞和间质细胞中呈弱阳性表达;CD44v6的表达与组织学分级、肿瘤大小、是否合并肝硬化、AFP表达、有无HBV感染等均无相关性。③VEGF-C和CD44v6表达在肝癌组织中的表达水平呈正相关(相关系数r=0.681,P<0.01)。
     结论:VEGF-C和CD44v6的表达与肿瘤侵袭转移的发生有关,可作为估计预后的指标,对判断肝癌的恶性程度,预测生物学行为具有一定的临床意义。
Objective:To investigate the expression of VEGF-C and CD44v6 in HCC and it's effect on the biological behavior of HCC.
     Methods:The expression of VEGF-C and CD44v6 in liver tissue specimens of 33 patients with HCC was detected by immunohistochemical staining.21 hepatic cirrhosis and 16 hepatic trauma or hepatic cyst were used as the control group.
     Results:1.The positive expression of VEGF-C in HCC tissues was located in cytoplasma of cancer cells.The incidence VEGF-C expression was 78.8%(26/33).Positive rates of VEGF-C expression in HCC tissue were significantly higher in HCC with metastasis than in HCC without metastasis(94.1% (16/17) vs 62.5%(10/16),P<0.05),but there were no significant correlation between the expression of VEGF-C and tumor size,tumor grade,AFP level,hepatic cirrhosis and HBV.2.The positive expression of CD44v6 in HCC tissues was located in membranes of cancer cells and partial cytoplasma.CD44v6 expression was found negative or weak positive in some lymphocytes and interstitial cells in trauma and cirrhosis groups.Strong positive CD44v6 expression was 72.7%(24/33) in HCC.Positive rates of CD44v6 expression in HCC tissue with metastasis were 94.1%(16/17), higher than those in HCC tissue without metastasis 50.0%(8/16),P<0.05.CD44v6 expression was not significantly related to tumor size,tumor grade,AFP level,hepatic cirrhosis and HBV.3.There was a close correlation between VEGF-C and CD44v6 in HCC(r=0.681,P<0.01).
     Conclusion:The expression of VEGF-C and CD44v6 was correlated with metastasis.VEGF-C and CD44v6 may be signs of aggressive phenotype for evaluating treatment and prognosis of HCC. Examination of expression these two proteins may be helpful to judge biological behavior of HCC.
引文
1 Sugimoto C, Saito A, Kikuzato M, et al. Angioechographic evaluation of tumor thrombi and the effect of transcatheter arterial embolization in patients with hepatocellular carcinoma [J]. J Gastroenterol, 2002, 37 (5) :363-368.
    
    2 Jeltsch M, Kaipainen A, Joukov V, et al. Hyperplasia of lymphatic vessels in VEGF-C transgenic mice. Science. 1997, 276 (5317): 1423-1425.
    
    3 Furudoi A, Tanaka S, Haruma K, et al. Clinical significance of vascular endothelial growth factor C expression and angiogenesis at the deepest invasive site of advanced colorectal carcinoma. Oncology. 2002, 62 (2): 157-166.
    
    4 Cao Y, Linden P, Farnebo J, et al. Vascular endothelial growth factor C induces angiogenesis in vivo. Proc Natl Acad Sci USA. 1998, 95 (24): 14389-14394.
    
    5 Tuhkanen AL, Tammi M, Tammi R. CD44 substituted with heparan sulfate and endo-beta-galactosidase-sensitive oligosaccharides: a major proteoglycan in adult human epidermis. J Invest Dermatol. 1997, 109 (2): 213-218.
    
    6 Tanabe KK, Ellis LM, Saya H. Expression of CD44R1 adhesion molecule in colon carcinomas and metastases. Lancet. 1993, 341 (8847): 725-726.
    
    7 Baker EA, Bergin FG, Leaper DJ. Plasminogen activator system, vascular endothelial growth factor, and colorectal cancer progression. Mol Pathol. 2000, 53 (6) :307-312.
    1Joukov V,PajusolaK,Kaipainen A,et al.A novel vascular endothelial growth factor,VEGF-C,is a ligand for the Flt4(VEGFR-3) and KDR(VEGFR-2) receptor tyrosine kinases.EMBO J.1996,15(7):1751.
    2Lee J,Gray A,Yuan J,et al.Vascular endothelial growth factor-related protein:a ligand and specific activator of the tyrosine kinase receptor Fit4.Proc Natl Acad Sci USA.1996,93(5):1988-1992.
    3Paavo,en K,Horelli-Kuitunen N,Chilov D,et al.Novel human vascular endothelial growth factor genes VEGF-B and VEGF-C localize to chromosomes 11q13 and 4q34,respectively.Circulation.1996,93(6):1079-1082.
    4Joukov V,KaipainenA,JeltschM,et al.Vascular endothelial growth factors VEGF-B and VEGF-C.J Cell Physiol.1997,173(2):211-215.
    5EichmannA,Corbel C,JaffredoT,et al.AvianVEGF-C:cloning,embryonic expression pattern and stimulation of the differentiation of VEGFR2-expressing endothelial cell precursors.Development.1998,125(4):743-752.
    6Furudoi A,Tanaka S,Haruma K,et al.Clinical significance of vascular endothelial growth factor C expression and angiogenesis at the deepest invasive site of advanced colorectal carcinoma.Oncology.2002,62(2):157-166.
    7洪长江,赵新国,钱学贤.VE6F家族新成员:VE6F-B、VEGF-C和VEGF-D.国外医学:生理病理科学与临床分册.1999,19(4):279-282.
    8陈自强,卞修武.血管内皮生长因子家族.国外医学:生理病理科学与临床分册.2000,20(3):187-189.
    9van Trappen PO,Pepper MS.Lymphatic dissemination of tumour cells and the formation of micrometastases.Lancet Oncol.2002,3(1):44-52.
    10Partanen TA,Arola J,Saaristo A,et al.VEGF-C and VEGF-D expression in neuroendocrine cells and their receptor,VEGFR-3,in fenestrated blood vessels in human tissues.FASEB J.2000,14(13):2087-2096.
    11Kleespies A,Guba M,Jauch KW,et al.Vascular endothelial growth factor in esophageal cancer.J Surg Oncol.2004,87(2):95-i04.
    12MakinenT,VeikkolaT,Mustjoki S,et al.Isolated lymphatic endothelial cells transduce growth,survival and migratory signals via the VEGF-C/D receptor VEGFR-3. EMBO J. 2001, 20(17): 4762-4773.
    
    13 Shalaby F, Rossant J, Yamaguchi TP, et al. Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature. 1995, 376(6535): 62-66.
    
    14 de Vries C, Escobedo JA, Ueno H, et al. The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. Science. 1992, 255(5047): 989-991.
    
    15 Goldberg MA, Schneider TJ. Similarities between the oxygen-sensing mechanisms regulating the expression of vascular endothelial growth factor and erythropoietin. J Biol Chem. 1994, 269(6): 4355-4359.
    
    16 Barleon B, Siemeister G, Martiny-Baron G, et al. Vascular endothelial growth factor up-regulates its receptor fms-like tyrosine kinase 1 (FLT-1) and a soluble variant of FLT-1 in human vascular endothelial cells. Cancer Res. 1997, 57(23): 5421-5425.
    
    17 Shibuya M. Vascular endothelial growth factor receptor-2: its unique signaling and specific ligand, VEGF-E. Cancer Sci. 2003, 94(9): 751-756.
    
    18 Takahashi T, Ueno H, Shibuya M. VEGF activates protein kinase C-dependent, but Ras-independent Raf-MEK-MAP kinase pathway for DNA synthesis in primary endothelial cells. Oncogene. 1999, 18(13): 2221-2230.
    
    19 Dimmeler S, Zeiher AM. Akt takes center stage in angiogenesis signaling. Circ Res. 2000, 86(1): 4-5.
    
    20 Jiang BH, Zheng JZ, Aoki M, et al. Phosphatidylinositol 3-kinase signaling mediates angiogenesis and expression of vascular endothelial growth factor in endothelial cells. Proc Natl Acad Sci USA. 2000, 97(4): 1749-1753.
    
    21 Waltenberger J, Claesson-Welsh L, Siegbahn A, et al. Different signal transduction properties of KDR and Fltl , two receptors for vascular endothelial growth factor. J Biol Chem. 1994, 269(43): 26988-26995.
    
    22 Gerber HP, McMurtrey A, Kowalski J, et al. Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3'-kinase/Akt signal transduction pathway. Requirement for Flk-1/KDR activation. J Biol Chem. 1998, 273(46): 30336-30343.
    
    23 Karkkainen MJ, Makinen T, Alitalo K. Lymphatic endothelium: a new frontier of metastasis research. Nat Cell Biol. 2002, 4(1): E2-E5.
    
    24 Kriehuber E, Breiteneder-Geleff S, Groeger M, et al. Isolation and characterization of dermal lymphatic and blood endothelial cells reveal stable and functionally specialized cell lineages. J Exp Med. 2001, 194(6): 797-808.
    
    25 Nathanson SD, Zarbo RJ, Wachna DL, et al. Microvessels that predict axillary lymph node metastases in patients with breast cancer. Arch Surg. 2000, 135 (5): 586-593.
    
    26 刘芳,张雅洁.血管内皮生长因子受体3.广州医学院学报,2002,30(2):73~75
    
    27 Jeltsch M, Kaipainen A, Joukov V, et al. Hyperplasia of lymphatic vessels in VEGF-C transgenic mice. Science. 1997, 276(5317): 1423-1425.
    
    28 Mandriota SJ, Jussila L, Jeltsch M, et al. Vascular endothelial growth factor-C-mediated lymphangiogenesis promotes tumour metastasis. EMBO J. 2001, 20(4): 672-682.
    
    29 Skobe M , Hawighorst T , Jackson DG , et al. Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nat Med. 2001, 7(2): 192-198.
    
    30 Skobe M, Hamberg LM, Hawighorst T, et al. Concurrent induction of lymphangiogenesis, angiogenesis, and macrophage recruitment by vascular endothelial growth factor-C in melanoma. Am J Pathol. 2001, 159(3): 893-903.
    
    31 Baldwin ME, Roufail S, Halford MM, et al. Multiple forms of mouse vascular endothelial growth factor-D are generated by RNA splicing and proteolysis. J Biol Chem. 2001, 276(47): 44307-44314.
    
    32 Krishnan J, Kirkin V, Steffen A, et al. Differential in vivo and in vitro expression of vascular endothelial growth factor (VEGF)-C and VEGF-D in tumors and its relationship to lymphatic metastasis in immunocompetent rats. Cancer Res. 2003, 63(3): 713-722.
    
    33 Mattila MM, Ruohola JK, Karpanen T, et al. VEGF-C induced lymphangiogenesis is associated with lymph node metastasis in orthotopic MCF-7 tumors. Int J Cancer. 2002, 98(6): 946-951.
    
    34 Fellmer PT, Sato K, Tanaka R, et al. Vascular endothelial growth factor-C gene expression in papillary and follicular thyroid carcinomas. Surgery. 1999, 126(6): 1056-1061.
    
    35 Tsurusaki T, Kanda S, Sakai H, et al. Vascular endothelial growth factor-C expression in human prostatic carcinoma and its relationship to lymph node metastasis. Br J Cancer. 1999, 80(1-2): 309-313.
    36 Ueda M, Terai Y, Yamashita Y, et al. Correlation between vascular endothelial growth factor-C expression and invasion phenotype in cervical carcinomas. Int J Cancer. 2002, 98(3): 335-343.
    
    37 Kajita T, Ohta Y, Kimura K, et al. The expression of vascular endothelial growth factor C and its receptors in non-small cell lung cancer. Br J Cancer. 2001, 85(2): 255-260.
    
    38 Akagi K, IkedaY, Miyazaki M, et al. Vascular endothelial growth factor-C (VEGF-C) expression in human colorectal cancer tissues. Br J Cancer. 2000, 83(7): 887-891.
    
    39 Hashimoto I, Kodama J, Seki N, et al. Vascular endothelial growth factor-C expression and its relationship to pelvic lymph node status in invasive cervical cancer. Br J Cancer. 2001, 85(1): 93-97.
    
    40 Duff SE, Li C, Jeziorska M, et al. Vascular endothelial growth factors C and D and lymphangiogenesis in gastrointestinal tract malignancy. Br J Cancer. 2003, 89(3): 426-430.
    
    41 Kinoshita J, Kitamura K, Kabashima A, et al. Clinical significance of vascular endothelial growth factor-C (VEGF-C) in breast cancer. Breast Cancer Res Treat. 2001, 66(2): 159-164.
    
    42 Kawakami M, Furuhata T, Kimura Y, et al. Quantification of vascular endothelial growth factor-C and its receptor-3 messenger RNA with real-time quantitative polymerase chain reaction as a predictor of lymph node metastasis in human colorectal cancer. Surgery. 2003, 133(3): 300-308.
    
    43 NakashimaT, KondohS, KitohH, et al. Vascular endothelial growth factor-C expression in human gallbladder cancer and its relationship to lymph node metastasis. Int J Mol Med. 2003, 11(1): 33-39.
    
    44 Hamada K, Oike Y, Takakura N, et al. VEGF-C signaling pathways through VEGFR-2 and VEGFR-3 in vasculoangiogenesis and hematopoiesis. Blood. 2000, 96(12): 3793-3800.
    
    45 Cao Y, Linden P, Farnebo J, et al. Vascular endothelial growth factor C induces angiogenesis in vivo. Proc Natl Acad Sci USA. 1998, 95(24): 14389-14394.
    
    46 Witzenbichler B, AsaharaT, MuroharaT, et al. Vascular endothelial growth factor-C (VEGF-C/VEGF-2) promotes angiogenesis in the setting of tissue ischemia. Am J Pathol. 1998, 153(2): 381-394.
    47 Valtola R, Salven P, Heikkila P, et al. VEGFR-3 and its ligand VEGF-C are associated with angiogenesis in breast cancer. Am J Pathol. 1999, 154(5): 1381-1390.
    
    48 Padera TP, Kadambi A, di Tomaso E, et al. Lymphatic metastasis in the absence of functional intratumor lymphatics. Science. 2002, 296(5574): 1883-1886.
    
    49 Mandriota SJ, Jussila L, Jeltsch M, et al. Vascular endothelial growth factor-C-mediated lymphangiogenesis promotes tumour metastasis. EMBO J, 2001, 20(4): 672-682.
    
    50 AmiokaT, Kitadai Y, TanakaS, et al. Vascular endothelial growth factor-C expression predicts lymph node metastasis of human gastric carcinomas invading the submucosa. Eur J Cancer. 2002, 38(10): 1413-1419.
    
    51 Amioka T, Kitadai Y, Tanaka S, et al. Vascular endothelial growth factor-C expression predicts lymph node metastasis of human gastric carcinomas invading the submucosa. Eur J Cancer. 2002, 38(10): 1413-1419.
    
    52 Kabashima A, Maehara Y, Kakeji Y, et al. Overexpression of vascular endothelial growth factor C is related to lymphogenous metastasis in early gastric carcinoma. Oncology. 2001, 60(2): 146-150.
    
    53 Ishikawa M, Kitayama J, Kazama S, et al. Expression of vascular endothelial growth factor C and D (VEGF-C and -D) is an important risk factor for lymphatic metastasis in undifferentiated early gastric carcinoma. Jpn J Clin Oncol. 2003, 33(1): 21-27.
    
    54 Maeda K, Yashiro M, Nishihara T, et al. Correlation between vascular endothelial growth factor C expression and lymph node metastasis in T1 carcinoma of the colon and rectum. Surg Today. 2003, 33(10): 736-739.
    
    55 Kim KJ, Li B, Winer J, et al. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature. 1993, 362(6423): 841-844.
    
    56 Makinen T, Jussila L, Veikkola T, et al. Inhibition of lymphangiogenesis with resulting lymphedema in transgenic mice expressing soluble VEGF receptor-3. Nat Med. 2001, 7(2): 199-205.
    
    57 Veikkola T, Jussila L, Makinen T, et al. Signalling via vascular endothelial growth factor receptor-3 is sufficient for lymphangiogenesis in transgenic mice. EMBO J. 2001, 20(6): 1223-1231.
    
    58 He Y, Kozaki K, Karpanen T, et al. Suppression of tumor lymphangiogenesis and lymph node metastasis by blocking vascular endothelial growth factor receptor 3 signaling. J Natl Cancer Inst. 2002, 94(11): 819-825.
    
    59 Eikesdal HP, Dahl O, Straume O, et al. Tumour angiogenesis and therapy directed at the neovasculature. Tidsskr Nor Laegeforen. 2004, 124(15): 1919-1922.
    
    60 Albelda SM, Buck CA. Integrins and other cell adhesion molecules. FASEB J.1990; 4(11): 2868-2880.
    
    61 Lamb RF, Hennigan RF, Turnbull K, et al. A AP-1-mediated invasion requires increased expression of the hyaluronan receptor CD44. Mol Cell Biol. 1997, 17(2): 963-976.
    
    62 Haynes BF, TelenMJ, Hele LP, et al. CD44—a molecule involved in leukocyte adherence and T-cell activation. Immunol Today. 1989, 10(12): 423-428.
    
    63 Fujita N, Yaegashi N, Ide Y, Sato S, et al. Expression of CD44 in normal human versus tumor endometrial tissues: possible implication of reduced expression of CD44 in lymph-vascular space involvement of cancer cells. Cancer Res, 1994, 54(14): 3922-3928.
    
    64 Hofmann M, Rudy W, Gunthert U, et al. A link between ras and metastatic behavior of tumor cells: ras induces CD44 promoter activity and leads to low-level expression of metastasis-specific variants of CD44 in CREF cells. Cancer Res. 1993, 53(7): 1516-1521.
    
    65 Spafford M, koeppe J, Pan Z, et al. Correlation of tumor markers p53, bcl-2, CD34, CD44H, CD44v6, and Ki-67 with survival and metastasis in laryngeal squamous cell carcinoma. Arch Otolaryngol Neck Surg. 1996, 122(6): 627-632.
    
    66 Culty M, Nguyen HA , Underhill CB. The hyaluronan receptor (CD44) participates in the uptake and degradation of hyaluronan. J Cell Biol. 1992, 116(4): 1055-1062.
    
    67 Cornil I, Theodorescu D, Man S, et al. Fibroblast cell interactions with human melanoma cells affect tumor cell growth as a function of tumor progression. Proc Natl Acad Sci USA.1991, 88(14): 6028-6032.
    
    68 Higashikawa K, Yokozaki H, Ue T, et al. Evaluation of CD44 transcription variants in human digestive tract carcinomas and normal tissues. Int J Cancer. 1996, 66(1): 11-17.
    
    69 Degrendele HC, kosfiszerM, Estess P, et al. CD44 activation and associated primary adhesion is inducible via T cell receptor stimulation. J Immunol, 1997, 159(6): 2549-2553.
    
    70 Tolg C, Hofmann M, Herrlich P, et al. Splicing choice from ten variant exons establishes CD44 variability. Nucleic Acids Res. 1993, 21 (5): 1225-1229.
    
    71 Ariza A, Mate JL, Isamat M etal. Standard and variant CD44 isoforms are commonly expressed in lung cancer of the non-small cell type but not of the small cell type. J Pathol. 1995, 177(4): 363-368.
    
    72 Heider KH, Hofmann M, Horst E, et al. A human homologue of the rat metastasis-associated variant of CD44 is expressed in colorectal carcinomas and adenomatous polyps. J Cell Biol. 1993 , 120(1): 227-233.
    
    73 Penno MB, August JT, Baylin SB, et al. Expression of CD44 in human lung tumors. Cancer Res.1994, 54(5): 1381-1387.
    
    74 Lu D, Tawfik O, Pantazis C, et al. Altered expression of CD44 and variant isoforms in human endocervix during progression. Gynecol Oncol, 1999, 75(1): 84-90.
    
    75 MathewJ, Hines JE, Obafunwa JO, et al. CD44 is expressed in hepatocellular carcinomas showing vascular invasion. J Pathol. 1996, 179(1): 74-79.
    76 Niitsu N, Iijima K. High serum soluble CD44 is correlated with a poor outcome of aggressive non-Hodgkin' s lymphoma. Leuk Res. 2002, 26(3): 241-248.
    
    77 曹卫东,章翔,刘飞,等.CD44在颅内转移瘤及脑胶质母细胞瘤中的表达研究,中华实验外科杂志,1999;16(5):398
    
    78 Pereira PA, Rubenthiran U, Kaneko M, et al. CD44s expression mitigates the phenotype of human colorectal cancer hepatic metastases. Anticancer Res. 2001, 21 (4A): 2713-2717.
    
    79 Chun SY, Bae OS, Kim JB. The significance of CD44 variants expression in colorectal cancer and its regional lymph nodes. J Korean Med Sci. 2000, 15(6): 696-700.
    
    80 Matsumura Y, Tarin D. Significance of CD44 gene products for cancer diagnosis and disease evaluation. Lancet.1992, 340(8827): 1053-1058.
    
    81 Kaufmann M, Heider KH, Sinn HP, et al. CD44 variant exon epitopes in primary breast cancer and length of survival. Lancet. 1995, 345(8950): 615-619.
    
    82 Berner HS, Nesland JM. Expression of CD44 isoforms in infiltrating lobular carcinoma of the breast. Breast Cancer Res Treat. 2001, 65(1): 23~29.
    
    83 Wielenga VJ, Heider KH, Offerhaus GJ, et al. Expression of CD44 variant proteins in human colorectal cancer is related to tumor progression. Cancer Res.1993,53(20):4754-4756.
    84Mulder JW,Kruyt PM,Sewnath M,et al.Colorectal cancer prognosis and expression of exon-v6-containing CD44 proteins.Lancet.1994,344(8935):1470-1472.
    85Yamaguchi A,Goi T,Seki K,et al.Clinical significance of combined immunohistochemical detection of CD44v and sialyl LeX expression for colorectal cancer patients undergoing curative resection.Oncology,1998:55(5):400-403.
    86Masson D,Denis MG,Lustenberger P.Limitations of CD44v6 amplification for the detection of tumour cells in the blood of colorectal cancer patients.Br J Cancer,2000,82(7):1283-1289.
    87Yamao T,Matsumura Y,Shimada Y,et al.Abnormal expression of CD44 variants in the exfoliated cells in the feces of patients with colorectal cancer.Gastroenterology.1998,114(6):1196-1205.
    88刘静贤,李吉龙,张培荣,等.大肠癌中CD44v6,P53,PCNA的表达及意义.肿瘤,2000,20(5):362.
    89Ham HJ,Ho LI,Chang JY,et al.Differential expression of the human metastasis adhesion molecule CD44V in normal and carcinomatous stomach mucosa of Chinese subjects.Cancer.1995,75(5):1065-1071.
    90Saito H,Tsujitani S,Katano K,etal.Serum concentration of CD44 variant 6 and its relation to prognosis in patients with gastric carcinoma.Cancer,1998,83(6):1094-1101.
    91Seiter S,Arch R,Reber S,et al.Prevention of tumor metastasis formation by anti-variant CD44.J Exp Med.1993,177(2):443-455.
    92毕爱华主编,医学免疫学.北京:人民军医出版社.1995:164-165.
    93Yanagisawa N,Mikami T,Mitomi H,et al.CD44 variant overexpression in gallbladder carcinoma associated with tumor dedifferentiation.Cancer.2001,91(2):408-416.
    94Ashida K,Terada T,Kitamura Y,et al.Expression of E-cadherin,alpha-catenin,beta-catenin,and CD44(standard and variant isoforms) in human cholangiocarcinoma:an immunohistochemical study.Hepatology.1998,2?(4):974-982.
    95Takigawa N,Segawa Y,Mandai K,et al.Serum CD44 levels in patients with non-small cell lung cancer and their relationship with clinicopathological features.Lung Cancer.1997,18(2):147-157.
    96Wimmel A,Kogan E,Ramaswamy A,et al.Variant expression of CD44 in preneoplastic lesions of the lung.Cancer.2001,92(5):1231-1236.
    97Tran TA,Kallakury BV,Sheehan CE,et al.Expression of CD44 standard form and variant isoforms in non-small cell lung carcinomas.Hum Pathol.1997,28(7):809-814.
    98吴玉泉,沈企周,马炬明,等.老年肺癌患者外周血CD44表达及其临床意义.临床肿瘤学杂志.2003,8(1):42.
    99Mizera-Nyczak E,Dyszkiewicz W,Heider KH,et al.Isoform expression of CD44 adhesion molecules,Bc1-2,p53 and Ki-67 proteins in lung cancer.Tumour Biol.2001,22(1):45-53.
    100Piffko J,Bankfalvi A,Klauke K,et al.Unaltered strong immunohistochemical expression of CD44-v6 and -v5 isoforms during development and progression of oral squamous cell carcinomas.J Oral Pathol Med.1996,25(9):502-506.
    101Dall P,Heider KH,Hekele A,et al.Surface protein expression and messenger RNA-splicing analysis of CD44 in uterine cervical cancer and normal cervical epithelium.Cancer Res.1994,54(13):3337-3341.
    102Yamaguchi A,Urano T,Goi T,et al.Expression of a CD44 variant containing exons 8 to 10 is a useful independent factor for the prediction of prognosis in colorectal cancer patients.J Clin Oncol.1996,14(4):1122-1127.
    103Morris SF,O'Hanlon DM,McLaughlin R,et al.The prognostic significance of CD44s and CD44v6 expression in stage two breast carcinoma:an immunohistochemical study.Eur J Surg Oncol.2001,27(6):527-531.
    104Tanabe KK,Ellis LM,Saya H.Expression of CD44R1 adhesion molecule in colon carcinomas and metastases.Lancet.1993,341(8847):725-726.
    105Hudson DL,Speight PM,Watt FM.Altered expression of CD44 isoforms in squamous-cell carcinomas and cell lines derived from them.Int J Cancer.1996,66(4):457-463.
    106Tuhkanen AL,Tammi M,Tammi R.CD44 substituted with heparan sulfate and endo-beta-galactosidase-sensitive oligosaccharides:a major proteoglycan in adult human epidermis.J Invest Dermatol.1997,109(2):213-218.
    107Trochon V,Mabilat C,Bertrand P,et al.Evidence of involvement of CD44in endothelial cell proliferation,migration and angiogenesis in vitro.Int J Cancer.1996,66(5):664-668.
    108Fasano M,Sabatini MT,Wieczored R,et al.CD44 and its v6 spliced variant in lung tumors:a role in histogenesis? Cancer.1997,80(1):34-41.
    109龙慧民,陈贻龄,郭震化,等.细胞粘附分子CD44的变异表达与肾癌的关系.中华外科杂志.1998,36(12):738.

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