HIF-1α和VEGF在垂体腺瘤中的表达和意义
摘要
目的:检测缺氧诱导因子-1α(HIF-1α)、血管内皮生长因子(VEGF)在侵袭性和非侵袭性垂体腺瘤中的表达,探讨其与肿瘤侵袭发生的关系及它们之间的相关性。
方法:采用免疫组化Envision二步法检测56例垂体腺瘤,其中32例侵袭性垂体腺瘤及24例非侵袭性垂体腺瘤标本中HIF-1α和VEGF的表达。
结果: HIF-1α在侵袭性垂体腺瘤中的强阳性及阳性表达率分别为53.1%和93.8%,明显高于非侵袭性垂体腺瘤中的16.7%和50.0%(P<0.01);VEGF在侵袭性垂体腺瘤中的强阳性及阳性表达率分别为56.3%和96.9%,明显高于非侵袭性垂体腺瘤中的12.5%和45.8%(P<0.01)。侵袭性腺瘤组中HIF-1α与VEGF的表达成正相关(P<0.01),非侵袭性腺瘤组中HIF-1α与VEGF的表达无明显相关性。
结论: HIF-1α、VEGF高表达与垂体腺瘤的侵袭性密切相关,可以作为判别垂体腺瘤侵袭性的有效参考指标。HIF-1α、VEGF在肿瘤侵袭及新生血管形成过程中可能存在协同作用。
Objective: To investigate the expressions of HIF-1αand VEGF in patients with invasive pituitary adenomas,and to evaluate the relationship between the expression of HIF-1αand VEGF,and the invasion of pituitary adenomas.
Methods: Immunohistochemical Envision method was used to determine the expressions of HIF-1αand VEGF in 56 cases of pituitary adenomas,32 cases were invasive and 24 were non-invasive patients with pituitary adenomas.
Result: The intense expression and expression rates of HIF-1αof pituitary adenomas patients with invasion were significantly higher than those without invasion(53.1% vs 16.7% and 93.8% vs 50.0%,p<0.01). The intense expression and expression rates of VEGF of pituitary adenomas patients with invasion were significantly higher than those without invasion(56.3% vs 12.5% and 96.9% vs 45.8%,p<0.01).There was a mutually positive correlation among HIF-1αand VEGF expressions in invasive pituitary adenomas(P<0.01),and no correlation among HIF-1αand VEGF expressions in non-invasive pituitary adenomas.
Conclusion: The high expression of HIF-1αand VEGF might relate to the aggressiveness and invasion in pituitary adenomass and may be useful markers for predicting invasiveness, and they might have close relationship in the invasiveness and angiogenesis of pituitary adenomas.
方法:采用免疫组化Envision二步法检测56例垂体腺瘤,其中32例侵袭性垂体腺瘤及24例非侵袭性垂体腺瘤标本中HIF-1α和VEGF的表达。
结果: HIF-1α在侵袭性垂体腺瘤中的强阳性及阳性表达率分别为53.1%和93.8%,明显高于非侵袭性垂体腺瘤中的16.7%和50.0%(P<0.01);VEGF在侵袭性垂体腺瘤中的强阳性及阳性表达率分别为56.3%和96.9%,明显高于非侵袭性垂体腺瘤中的12.5%和45.8%(P<0.01)。侵袭性腺瘤组中HIF-1α与VEGF的表达成正相关(P<0.01),非侵袭性腺瘤组中HIF-1α与VEGF的表达无明显相关性。
结论: HIF-1α、VEGF高表达与垂体腺瘤的侵袭性密切相关,可以作为判别垂体腺瘤侵袭性的有效参考指标。HIF-1α、VEGF在肿瘤侵袭及新生血管形成过程中可能存在协同作用。
Objective: To investigate the expressions of HIF-1αand VEGF in patients with invasive pituitary adenomas,and to evaluate the relationship between the expression of HIF-1αand VEGF,and the invasion of pituitary adenomas.
Methods: Immunohistochemical Envision method was used to determine the expressions of HIF-1αand VEGF in 56 cases of pituitary adenomas,32 cases were invasive and 24 were non-invasive patients with pituitary adenomas.
Result: The intense expression and expression rates of HIF-1αof pituitary adenomas patients with invasion were significantly higher than those without invasion(53.1% vs 16.7% and 93.8% vs 50.0%,p<0.01). The intense expression and expression rates of VEGF of pituitary adenomas patients with invasion were significantly higher than those without invasion(56.3% vs 12.5% and 96.9% vs 45.8%,p<0.01).There was a mutually positive correlation among HIF-1αand VEGF expressions in invasive pituitary adenomas(P<0.01),and no correlation among HIF-1αand VEGF expressions in non-invasive pituitary adenomas.
Conclusion: The high expression of HIF-1αand VEGF might relate to the aggressiveness and invasion in pituitary adenomass and may be useful markers for predicting invasiveness, and they might have close relationship in the invasiveness and angiogenesis of pituitary adenomas.
引文
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[1] Suhardja A,Kovacs K,Rutka J.Genetic basis of pituitary adenoma invasiveness a review [J].J Neurooncol,2001,52(3):195-204.
[2] Neto AG, McCutcheon IE, Vang R,et al. Elevated expression of p21 (WAF1/Cip1) in hormonally active pituitary adenomas[J].Ann Diagn Pathol, 2005, 9(1):6-10.
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[5] Zhu X, Lee K, Asa SL, et a1.Epigenetic silencing through DNA and histone methylation of fibroblast growth factor receptor 2 in neoplastic pituitary cells [J].Am J Pathol,2007,170 (5):1618-28.
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[10] Pan LX, Chen ZP, Liu YS,et a1. Magnetic resonance imaging and biological markers in pituitary adenomas with invasion of the cavernous sinus space[J]. J Neurooncol,2005,74 (1):71-6.
[11] Verges B,Boureille F,Goudet P,et a1.Pituitary disease in MEN type l(MEN-1):data from the France-Belgium MEN-1 multicenter study[J].J Clin Endocrinol Metab,2002,87(2):457- 465.
[12] Yi J,Yu D,Chen Y,et a1.P16 overexpression in pituitary adenomas by immunohistochemistry and in situ hybridization[J].Chin Med J (Eng),2000,l13(2):162-166.
[13]姜福全,岳志健,周晓平,等.PTEN蛋白在垂体瘤中的表达及其意义[J].第二军医大学学报,2003,24(8):847-849.
[14]高建国,范月超,张华秋,等. PTEN蛋白和CyclinD1在垂体瘤中的表达和相关性研究[J].中国肿瘤临床,2005,32(11):601-603.
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[22] Yoshida D,Kim K,Noha M,et a1.Anti-apoptotic action by hypoxia inducible factor-l alpha in human pituitary adenomas cell line,HP-75 in hypoxic condition[J].J Neurooncol,2006, 78(3):217-225.
[23]张晨冉,孙青芳,卞留贯,等.缺氧诱导因子-1α和血管内皮生长因子与垂体腺瘤侵袭性的研究[J].中华神经外科疾病研究杂志,2008,7(2):100-104.
[24] Pawlikowski M, Gruszka A, Kurnatowska I, et a1.Proliferating cell nuclear antigen (PCNA) expression in pituitary adenomas: relationship to the endocrine phenotype of adenoma [J]. Folia Histochem Cytobiol,2006,44(1):37-41.
[2] Takada K,Yamada S,Teramoto A.Correlation between tumor vnscularity and clinical findings in patients with pituitary adenomns[J].Endor Pathol,2004,15(2):131-139.
[3] Suhardja A,Kovacs K,Rutka J.Genetic basis of pituitary adenoma invasiveness:a review[J].J Neurooncol,2001,52(3):195-204.
[4] McCutcheon IE, Vang R,et al. Elevated expression of p21 (WAF1/Cip1) in hormonally active pituitary adenomas[J].Ann Diagn Pathol, 2005, 9(1):6-10.
[5] Giacomini D, Páez-Pereda M, Refojo D, et al. New mechanisms involved in the pathogenesis of pituitary adenomas [J]. Medicina (B Aires),2003,63(2):147-50.
[6] McCabe CJ,Khaira JS,Boelaert K,et a1.Expression of pituitary tumour transforming gene (PTTG) and fibroblast growth factor-2 (FGF-2) in human pituitary adenomas:relationships to clinical tumour behaviour[J].Clin Endocrinol(Oxf),2003,58(2):141-150.
[7] Zhu X, Lee K, Asa SL, et a1.Epigenetic silencing through DNA and histone methylation of fibroblast growth factor receptor 2 in neoplastic pituitary cells [J]. Am J Pathol,2007,170 (5): 1618-28.
[8] Hussaini IM, Trotter C, Zhao Y, et a1. Matrix metalloproteinase-9 is differentially expressed in nonfunctioning invasive and noninvasive pituitary adenomas and increases invasion in human pituitary adenoma cell line[J].Am J Pathol, 2007,170(1):356-65.
[9] Simpson DJ,Bicknell EJ,Buch HN,et a1.Genome-wide amplification and allelotyping of sporadic pituitary adenomas identify novel regions of genetic loss[J].Genes Chromosomes Cancer,2003,37(3):225-236.
[10] Gejman R, Swearingen B, Hedley-Whyte ET,et a1. Role of Ki-67 proliferation index and p53 expression in predicting progression of pituitary adenomas[J].Hum Pathol,2008,39 (5): 758- 66.
[11] Pan LX, Chen ZP, Liu YS,et a1. Magnetic resonance imaging and biological markers in pituitary adenomas with invasion of the cavernous sinus space[J]. J Neurooncol,2005,74 (1): 71-6.
[12] Verges B,Boureille F,Goudet P,et a1.Pituitary disease in MEN type l(MEN-1):data from the France-Belgium MEN-1 multicenter study[J].J Clin Endocrinol Metab,2002,87(2):457 -465.
[13] Yi J,Yu D,Chen Y , et a1.P16 overexpression in pituitary adenomas by immunohistochemistry and in situ hybridization[J].Chin Med J (Eng),2000,113 (2 ):162-166.
[14]姜福全,岳志健,周晓平,等.PTEN蛋白在垂体瘤中的表达及其意义[J].第二军医大学学报,2003,24(8):847-849.
[15]Honegger J,Prettin C,Feuerhake,et al. Expression of Ki-67 antigen in nonfunctioning pituitary adenomas:correlation with growth velocity and invasiveness[J]. Neurosurgey,2003,99(4):674-679.
[16]张龙,雷霆,薛德麟.EGF,Genistein对垂体瘤细胞膜PI转换的影响[J].中国肿瘤生物治疗杂志,2002,9(4):252.
[17] Pawlikowski M, Gruszka A, Kurnatowska I, et a1.Proliferating cell nuclear antigen (PCNA) expression in pituitary adenomas: relationship to the endocrine phenotype of adenoma [J].Folia Histochem Cytobiol,2006,44(1):37-41.
[18] Vidal S,Horvath E,Kovacs K,et a1.Expression of hypoxia-inducible factor-lα(HIF-lα) in pituitary tumors[J].Histol Histopathol,2003,18(3):679-686.
[19] Yoshida D,Kim K,Noha M,et a1.Anti-apoptotic action by hypoxia inducible factor-l alpha in human pituitary adenomas cell line,HP-75 in hypoxic condition[J].J Neurooncol, 2006,78(3):217-225.
[20]曲鑫,曲元明,张泽香,等.CD147、MMP-9和VEGF在垂体腺瘤中的表达及与其生物学行为的关系[J].山东大学学报(医学版),2008,46(3):288-291.
[21] Kuwai T,Kitadai Y,Tanka S,et a1.Expression of hypoxia inducible factor-1αis associated with tumor vascularizaton in human colotectalcarcinoma[J].Int J Cancer,2003, l05 (2): 176 -181.
[22] Veikkola T,Alitalo K.VEGFs,receptors and angiogenesis[J].Semin Cancer Biol, 1999, 9:211- 220.
[23] Forsythe J A,Bing H J,Narayan V,et a1.Activation of Vascular Endothelial Growth Factor Gene Transcription by Hypoxia Inducible Factor l[J].Molecular and Cellular Biology,1996,16(9):4604-4613.
[24] Knosp E,Steiner E,Kitz K,et a1.Pituitary adenomas with invasion of the cavernous sinus space:a magnetic resonance imaging classification compared with surgical findings [J]. Neurosurgery,1993,33(4):610-618.
[25] Wilson CB.A decade of pituitary microsurgery:The herbert olivercrona lecture[J]. J Nenurosury, 1984,61(5):814-833.
[26] Carron CP,Meyer DM,Pegg JA ,et a1.A Peptidon in eticantagonist of the intergrin alpha (v)beta 3 inhibitis leyding cell tumor growth and develvopment of hypercalcemia of malignancy[J].Cancer Res,1998,58(9):1930.
[27] Semenza GL,Wang GL.A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation [J].Mol CellBiol,1992,12:5447-5454.
[28] Semenza GL. Hypoxia,clonal selection,and the role of HIF-1 in tumor progression[J].Crit Rev Biochem Mol Biol,2000,35(2):71-103.
[29]Semenza GL.HIF-1 and mechanisms of hypoxia sensing[J].Curr Opin Cell Biol,2001,13 (2) 167-71.
[30]袁玉锋,刘志苏,何跃明,等.Ang2、HIF-1及VEGF对肝癌血管形成的影响[J].中国普通外科杂志,2006,15(7):525-528.
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