原发性肝癌中Glypican-3蛋白和C-myb蛋白的表达及其临床病理意义
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摘要
目的研究磷脂酰肌醇蛋白聚糖3 (Glypican-3)和原癌基因C-myb在原发性肝癌(Primary Hepatic Carcinoma, PHC)组织中的表达情况,探讨它们之间的相互关系以及它们与原发性肝癌临床病理特征之间的关系。
方法收集中南大学湘雅二医院肝胆胰外科2001年1月至2006年12月经手术切除及病理证实的原发性肝癌标本50例(术前均未进行化疗和放疗)及15例癌旁组织(距癌肿≥3cm)为对照,经10%甲醛固定后常规石蜡包埋连续切片,切片厚3μm,应用免疫组化SP法分别检测癌组织及癌旁组织的Glypican-3蛋白和C-myb蛋白的表达情况,并于高倍镜下评分。
结果Glypican-3蛋白在原发性肝癌的癌组织中有表达,在癌旁组织中未见表达,C-myb蛋白在原发性肝癌的癌组织和癌旁组织均有表达,且原发性肝癌组织中Glypican-3蛋白和C-myb蛋白的阳性表达率和表达评分与癌旁组织相比均具有显著的统计学差异(P<0.01,P<0.05)。
Glypican-3蛋白表达与年龄、性别、肝癌病理类型、病理分级、乙肝表面抗原、血清AFP水平、肝硬化程度、有无转移、有无门静脉癌栓、肿瘤大体形态、肿块直径无明显相关(P>0.05)。
C-myb蛋白在有肝内转移、有门静脉癌栓形成组中的阳性表达率及表达评分明显高于无肝内外转移、无门静脉癌栓形成组,差异有统计学意义(P<0.05)。而C-myb蛋白表达与年龄、性别、肝癌病理类型、病理分级、乙肝表面抗原、血清AFP水平、肝硬化程度、肿瘤大体形态、肿块直径无明显相关(P>0.05)。
原发性肝癌组织中Glypican-3蛋白和C-myb蛋白的表达评分无明显关联(r=0.23,P>0.05)。
结论1、Glypican-3蛋白在PHC癌组织中的高表达,而在癌旁肝脏组织中未见表达,表现出Glypican-3良好的敏感性和特异性,有望成为早期肝癌,尤其是AFP阴性的肝癌的诊断指标。
2、C-myb蛋白在PHC癌组织中的表达明显高于癌旁肝脏组织,且其可能在PHC的侵袭转移中发挥了作用,可能是肝癌的不良预后因素,可能作为判断肝癌恶性程度的一个预测指标
3、Glypican-3蛋白和C-myb蛋白在PHC组织中的表达不存在相关性,提示Glypican-3蛋白和C-myb蛋白在原发性肝癌的发生、发展中不存在明显关系。
Objective To investigate the expression of Glypican-3 (GPC3) protein and proto-oncogene C-myb protein in Primary Hepatic Carcinoma (PHC), and to explore the relationships of themselves and the correlation between them.
Methods The specimens from 50 patients with Primary Hepatic Carcinoma (PHC) and 15 corresponding paraneoplastic hepatic tissues were fixed in 10% formalin and routinely embedded in paraffin. The specimens were continuously sliced into 3μm-thick sections. The expressions of Glypican-3 and C-myb were detected by immunohistochemistry SP method and scored under high-power microscopy.
Results There are significantly statistical distinctions in the expressive positive rate and the expressive scores of Glypican-3 and C-myb protein between cancer tissues and paraneoplastic tissues (P<0.01, P<0.05)
We haven't found the relatioships between Glypican-3 and main clinicopathological characteristics of PHC(P>0.05).
There is no correlation between the expression of CAI protein and clinicopathological characteristics of PHC, except that the expressive positive rate and the expressive scores of PHC significantly higher with intrahepatic metatasis and tumor thrombosis than those which were without metastasis and tumor thrombosis.(P<0.05).
There is no evident correlation between the expressive scores of Glypican-3 protein and that of C-myb protein in cancer tissues of PHC (r =0.23, P>0.05)
Conclusion
1. The high expression of Glypican-3 protein in PHC may play an impotant role in the diagnosis of PHC because of its sensitivity and especiallity.
2. The expression of C-myb palys an important role in the invasive and metastatic part of PHC.It may be a harmful factor of prognosis.
3. there is no correlation between the expressive scores of Glypican-3 protein and C-myb protein in cancer tissues of PHC
方法收集中南大学湘雅二医院肝胆胰外科2001年1月至2006年12月经手术切除及病理证实的原发性肝癌标本50例(术前均未进行化疗和放疗)及15例癌旁组织(距癌肿≥3cm)为对照,经10%甲醛固定后常规石蜡包埋连续切片,切片厚3μm,应用免疫组化SP法分别检测癌组织及癌旁组织的Glypican-3蛋白和C-myb蛋白的表达情况,并于高倍镜下评分。
结果Glypican-3蛋白在原发性肝癌的癌组织中有表达,在癌旁组织中未见表达,C-myb蛋白在原发性肝癌的癌组织和癌旁组织均有表达,且原发性肝癌组织中Glypican-3蛋白和C-myb蛋白的阳性表达率和表达评分与癌旁组织相比均具有显著的统计学差异(P<0.01,P<0.05)。
Glypican-3蛋白表达与年龄、性别、肝癌病理类型、病理分级、乙肝表面抗原、血清AFP水平、肝硬化程度、有无转移、有无门静脉癌栓、肿瘤大体形态、肿块直径无明显相关(P>0.05)。
C-myb蛋白在有肝内转移、有门静脉癌栓形成组中的阳性表达率及表达评分明显高于无肝内外转移、无门静脉癌栓形成组,差异有统计学意义(P<0.05)。而C-myb蛋白表达与年龄、性别、肝癌病理类型、病理分级、乙肝表面抗原、血清AFP水平、肝硬化程度、肿瘤大体形态、肿块直径无明显相关(P>0.05)。
原发性肝癌组织中Glypican-3蛋白和C-myb蛋白的表达评分无明显关联(r=0.23,P>0.05)。
结论1、Glypican-3蛋白在PHC癌组织中的高表达,而在癌旁肝脏组织中未见表达,表现出Glypican-3良好的敏感性和特异性,有望成为早期肝癌,尤其是AFP阴性的肝癌的诊断指标。
2、C-myb蛋白在PHC癌组织中的表达明显高于癌旁肝脏组织,且其可能在PHC的侵袭转移中发挥了作用,可能是肝癌的不良预后因素,可能作为判断肝癌恶性程度的一个预测指标
3、Glypican-3蛋白和C-myb蛋白在PHC组织中的表达不存在相关性,提示Glypican-3蛋白和C-myb蛋白在原发性肝癌的发生、发展中不存在明显关系。
Objective To investigate the expression of Glypican-3 (GPC3) protein and proto-oncogene C-myb protein in Primary Hepatic Carcinoma (PHC), and to explore the relationships of themselves and the correlation between them.
Methods The specimens from 50 patients with Primary Hepatic Carcinoma (PHC) and 15 corresponding paraneoplastic hepatic tissues were fixed in 10% formalin and routinely embedded in paraffin. The specimens were continuously sliced into 3μm-thick sections. The expressions of Glypican-3 and C-myb were detected by immunohistochemistry SP method and scored under high-power microscopy.
Results There are significantly statistical distinctions in the expressive positive rate and the expressive scores of Glypican-3 and C-myb protein between cancer tissues and paraneoplastic tissues (P<0.01, P<0.05)
We haven't found the relatioships between Glypican-3 and main clinicopathological characteristics of PHC(P>0.05).
There is no correlation between the expression of CAI protein and clinicopathological characteristics of PHC, except that the expressive positive rate and the expressive scores of PHC significantly higher with intrahepatic metatasis and tumor thrombosis than those which were without metastasis and tumor thrombosis.(P<0.05).
There is no evident correlation between the expressive scores of Glypican-3 protein and that of C-myb protein in cancer tissues of PHC (r =0.23, P>0.05)
Conclusion
1. The high expression of Glypican-3 protein in PHC may play an impotant role in the diagnosis of PHC because of its sensitivity and especiallity.
2. The expression of C-myb palys an important role in the invasive and metastatic part of PHC.It may be a harmful factor of prognosis.
3. there is no correlation between the expressive scores of Glypican-3 protein and C-myb protein in cancer tissues of PHC
引文
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[1]Pilia QHughes Benzie RM,MacKenzie A, et al.Mutations in GPC3,a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome[J]. Nat Genet,1996,12(3):241-247.
[2]周学平,王红阳,杨广顺,等。米托蒽醒抗性基因在人肝癌组织中的表达。中华外科杂志,1999；37(3)：172-173
[3]周学平,王红阳,等。MXR7基因的克隆及其在正常和肿瘤组织中的表达。中华实验外科杂志,1999；16(2)：144-146
[4]Dvaid QLories V,DecoekB,et al Molecula celoning of a PhosP atidylinositol-anhored membrnane haparan sulfate proteoglycan from human lung fibroblasts.J Cell Biol 1990;111(6 Pt2):3165-3176.
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[10]Paine-Saunders S, Vivinao BL, Saunders S.GPC6, a novel member of glypican gene family, encodes a prorduct structurally related to GPC4 and is colocalized with GPC5 on human chromosome 13.Genomics 1999;1;57(3):455-458.
[11]Jogre F,Scott BS.Glypican:proteoglucans with a surprise. J Clin Invest 2001:108(4):497-501.
[12]eugelers M,De Cat B,Ceulemans H, et al. Glypican-6,a new member of the glypican family of cell surface heparan sulfate proteoglycans[J]. J Biol Chem,1999,274 (38):26968-26977.
[13]risaru S, Canuci J, Tee J, et al.Glypican-3 modulates BMP-and FGF-mediated effects during renal branching morphogenesis [J]. Dev Biol,2001,231: 31
[14]Jackson SM,Nakato H, SugiuraM, et al.Dally, a Drosophila glypican,controls cellular response to the TGF-bata-related morphogen Dpp[J].Development,1997,124:113
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[38]Farooq M, Hwang SY,Park MK,et al. Blocking endogenous Glypican-3 expression releases from G1 arrest[J].Mol.Cell,2003.15(3):356-60.
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[41]Paine-Saunders S., Viviano BL, Zupicich J, et al. Glypican-3 controls cellular responses to Bmp4 in limb patterning and skeletal development[J].Dev. Biol. 2000,225:179-87.
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[45]Topczewsky J, Sepich DS, Myers DC, et al.The Zebrafish Glypican Knypek controls cell polarity during gastrulation movements of convergent extension[J].Dev Cell,2001,1:251-64.
[46]Baeg GH, Lin X, Khare N, et al.Heparan sulfate proteoglycans are critical for the organization of the extracellular distribution of Wingless[J].Development, 2001,128:87-94.
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[48]Baeg GH, Perrimon N. Functional binding of secreted molecules to heparan sulfate proteoglycans in Drosophila[J].Curr Opin Cell Biol,2000,12:575-80.
[49]Capurro MI, Wen Shi, Sandal S, et al. Processing by Convertases Is Not Required for Glypican-3-induced Stimulation of Hepatocellular Carcinoma Growth[J].The journal of biological chemistry,2005,280(50):41201-06.
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[66]Ness SA.Myb binging proteins regulators and cohorts in transformation. Oncogene,1999;18(19):3039.
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[1]Pilia QHughes Benzie RM,MacKenzie A, et al.Mutations in GPC3,a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome[J]. Nat Genet,1996,12(3):241-247.
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