肝门部胆管癌MR表现与MVD、VEGF表达的相关性研究
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摘要
目的分析肝门部胆管癌(hilar cholangiocarcinoma, HC)MRI表现与微血管密度(microvessel density, MVD)、血管内皮生长因子(vascular endothelial growth factor, VEGF)表达之间的相关性,探讨MRI预测肿瘤血管生成、肿瘤生物学行为及其预后的价值。
方法28例HC患者行MRI检查(年龄43～75岁,平均56.23岁),在MRI检查1周内手术治疗,15例行根治性切除,13例行剖腹探查姑息性切除。实验分组:正常胆管组织取自9例肝细胞肝癌癌旁1～2cm的汇管区胆管上皮组织;癌旁组织取自15例根治性切除标本的癌旁1～2cm的肝组织;肿瘤组织取自28例HC的手术切除标本。所有标本均经病理组织学证实,其中管状腺癌16例、未分化癌8例、黏液腺癌3例、乳头状腺癌1例。所有病理标本均行免疫组织化学检查分析其MVD、VEGF表达;运用统计学方法分析各实验组间MVD、VEGF表达的差异性,及MRI形态学特征、动态增强早期信号强度增强率(△SI)与MVD、VEGF表达的相关性。
结果(1)MR表现:28例HC均可见肝门肿块、肝内胆管扩张、肝门胆管中断,其中浸润型20例,外生型7例,管内型1例。病灶在T1WI均呈低信号,在T2WI呈等或稍高信号。依据动态增强不同强化模式分:I型18例、II型6例、III型3例、IV型1例。3D-DCE-MRA中肝动脉示螺旋样改变4例,局限性狭窄2例;门静脉受侵18例,表现为门脉侧壁浸润、门脉狭窄或闭塞。
(2)免疫组织化学检测MVD、VEGF表达: MVD、VEGF表达在胆管癌组织和癌旁组织中的水平明显高于正常组织(P<0.01)。在癌组织、癌旁组织和正常组织共52例标本中,20例VEGF表达阴性,其平均MVD值为17.42±11.13,32例VEGF表达阳性,其平均MVD值为33.15±8.29,VEGF阳性表达组的MVD水平明显高于阴性组,此差异具有显著性意义(P<0.05)。MVD、VEGF的表达与HC的组织学类型无统计学意义(P>0.05),不同的组织学类型中,MVD、VEGF表达随着分化程度的增高而降低,但差异无统计学意义(P>0.05)。
(3)MR形态学表现中,肿瘤生长方式的分型与MVD、VEGF表达无明显相关性(P>0.05)。血管受侵组的MVD、VEGF表达明显高于无血管受侵组;神经浸润组的MVD、VEGF表达明显高于无神经浸润组;淋巴结转移组的MVD、VEGF表达明显高于无淋巴结转移组,以上均具有统计学意义(P<0.05)。病灶内有扩张的胆管与无扩张的胆管组间MVD、VEGF表达无明显差异(P>0.05)。MR动态增强扫描中,ΔSI与MVD呈明显正相关,与VEGF的表达亦呈正相关性。
结论(1)MR具备多组织成像能力,包括MRI、MRCP、MR动态增强和3D-DCE-MRA,能较好显示HC的影像学特征及其对血管、胆管和邻近结构的侵犯,可对HC进行准确的诊断,对临床制定正确的治疗方案具有指导意义。(2)肿瘤血管形成在肝门部胆管癌的发生发展中起了重要的作用,高水平的MVD及VEGF提示预后不良。(3)MR形态学特征、动态增强△SI在反映HC的病理特征、VEGF表达水平、推测微血管密度等方面具有潜在作用,作为一种非创伤性检查技术,可在一定程度上反映肿瘤血管生成情况,有助于判断肿瘤的生物学行为和预后。
Objective To analysis the correlation of MR findings with MVD and expression of VEGF in hilar cholangiocarcinoma, and to explore the value of MR Imaging in estimating the degree of neoangiogenesis, biologic behavior and prognosis of hilar cholangiocarcinoma.
Materials and methods magnetic resonance (MR) imaging of hilar cholangiocarcinoma was performed in Twenty-eight patients (aged 43～75 years, mean age 56.23 years) .In all selected patients, 15 cases received radical operation and the others received palliative operation. Experiment group: the normal tissues were from 9 cases of hepatic carcinoma; the para-tumor tissues were from the incising margin of radical operation and tumor tissues were from 28 cases operative specimens. all lesions were verified by pathological and immunochemical methods, including 16 cases of tubular adenocarcinoma, 8 cases of non-differentiated adenocarcinoma, 3 cases of mucinous adenocarcinoma, 1 cases of mastoid adenocarcinoma. The correlation of MR findings and dynamic contrast-enhanced MR Imaging△SI with MVD and expression of VEGF in hilar cholangiocarcinoma were analyzed.
Results (1)MR imaging findings: Hilar mass, dilatation of intrahepatic ducts and discontinuniy of hilar biliary ducts were seen in all cases, including 20 infiltrating, 7 exophytic and 1 intraluminal lesions. All the tumors were hypintense on T1-weighted spin-echo images. Most of the tumors presented iso- or mild hyper-intensity on T2-weighted images. According the different types of dynamic contrast-enhanced MR Imaging: 18 cases of I type、6 cases of II type、3 cases of III type and 1 cases of IV type. Spiral-like arteries were demonstrated in 4 cases and located strait in 2 cases on 3D-DCE-MRA during arterial phase. Portal vein was involved in 18 cases, presenting as infiltration, encasement or occlusion of the vein.
(2)MVD and VEGF expression detected by immunochemical methods: The MVD in tumor tissue and para-tumor tissue was significantly higher than in normal tissue(P<0.01).In 52 cases of normal tissues and tumor tissues, VEGF positive expression were found in 32 cases, and the mean MVD was 33.15±8.29; VEGF negative expression were found in 20 cases, and the mean MVD was 17.42±11.13. The difference between MVD、VEGF expression and histological type had no statistical significance (P>0.05).
(3)MVD in the groups of invasion and metastases in the lesions were higher than non-metastases (P<0.05); but their relation to the morphologic classification according to growth pattern were not significant (P>0.05) .There was correlation between MVD and dynamic enhancement pattern (P<0.05) ; the enhancement rate (△SI) of the early-phase signal intensity was significantly correlated with MVD and VEGF.
Conclusions (1)MR, including plain MR, MRCP , dynamic contrast-enhanced MRI and 3D-DCE-MRA ,can give more useful information about the diagnosis and preoperative evaluation in hilar cholangiocarcinoma.
(2)hilar cholangiocarcinoma progression was angiogenesis-correlation, and higher MVD and VEGF expression indicated poor prognosis.
(3)MR imaging findings and dynamic contrast-enhanced MR△SI is of potential value for estimating the degree of tumor angiogenesis, biologic behavior and prognosis of hilar cholangiocarcinoma. In some sense, MRI may estimate the degree of tumor angiogenesis, biologic behavior and prognosis of hilar cholangiocarcinoma.
方法28例HC患者行MRI检查(年龄43～75岁,平均56.23岁),在MRI检查1周内手术治疗,15例行根治性切除,13例行剖腹探查姑息性切除。实验分组:正常胆管组织取自9例肝细胞肝癌癌旁1～2cm的汇管区胆管上皮组织;癌旁组织取自15例根治性切除标本的癌旁1～2cm的肝组织;肿瘤组织取自28例HC的手术切除标本。所有标本均经病理组织学证实,其中管状腺癌16例、未分化癌8例、黏液腺癌3例、乳头状腺癌1例。所有病理标本均行免疫组织化学检查分析其MVD、VEGF表达;运用统计学方法分析各实验组间MVD、VEGF表达的差异性,及MRI形态学特征、动态增强早期信号强度增强率(△SI)与MVD、VEGF表达的相关性。
结果(1)MR表现:28例HC均可见肝门肿块、肝内胆管扩张、肝门胆管中断,其中浸润型20例,外生型7例,管内型1例。病灶在T1WI均呈低信号,在T2WI呈等或稍高信号。依据动态增强不同强化模式分:I型18例、II型6例、III型3例、IV型1例。3D-DCE-MRA中肝动脉示螺旋样改变4例,局限性狭窄2例;门静脉受侵18例,表现为门脉侧壁浸润、门脉狭窄或闭塞。
(2)免疫组织化学检测MVD、VEGF表达: MVD、VEGF表达在胆管癌组织和癌旁组织中的水平明显高于正常组织(P<0.01)。在癌组织、癌旁组织和正常组织共52例标本中,20例VEGF表达阴性,其平均MVD值为17.42±11.13,32例VEGF表达阳性,其平均MVD值为33.15±8.29,VEGF阳性表达组的MVD水平明显高于阴性组,此差异具有显著性意义(P<0.05)。MVD、VEGF的表达与HC的组织学类型无统计学意义(P>0.05),不同的组织学类型中,MVD、VEGF表达随着分化程度的增高而降低,但差异无统计学意义(P>0.05)。
(3)MR形态学表现中,肿瘤生长方式的分型与MVD、VEGF表达无明显相关性(P>0.05)。血管受侵组的MVD、VEGF表达明显高于无血管受侵组;神经浸润组的MVD、VEGF表达明显高于无神经浸润组;淋巴结转移组的MVD、VEGF表达明显高于无淋巴结转移组,以上均具有统计学意义(P<0.05)。病灶内有扩张的胆管与无扩张的胆管组间MVD、VEGF表达无明显差异(P>0.05)。MR动态增强扫描中,ΔSI与MVD呈明显正相关,与VEGF的表达亦呈正相关性。
结论(1)MR具备多组织成像能力,包括MRI、MRCP、MR动态增强和3D-DCE-MRA,能较好显示HC的影像学特征及其对血管、胆管和邻近结构的侵犯,可对HC进行准确的诊断,对临床制定正确的治疗方案具有指导意义。(2)肿瘤血管形成在肝门部胆管癌的发生发展中起了重要的作用,高水平的MVD及VEGF提示预后不良。(3)MR形态学特征、动态增强△SI在反映HC的病理特征、VEGF表达水平、推测微血管密度等方面具有潜在作用,作为一种非创伤性检查技术,可在一定程度上反映肿瘤血管生成情况,有助于判断肿瘤的生物学行为和预后。
Objective To analysis the correlation of MR findings with MVD and expression of VEGF in hilar cholangiocarcinoma, and to explore the value of MR Imaging in estimating the degree of neoangiogenesis, biologic behavior and prognosis of hilar cholangiocarcinoma.
Materials and methods magnetic resonance (MR) imaging of hilar cholangiocarcinoma was performed in Twenty-eight patients (aged 43～75 years, mean age 56.23 years) .In all selected patients, 15 cases received radical operation and the others received palliative operation. Experiment group: the normal tissues were from 9 cases of hepatic carcinoma; the para-tumor tissues were from the incising margin of radical operation and tumor tissues were from 28 cases operative specimens. all lesions were verified by pathological and immunochemical methods, including 16 cases of tubular adenocarcinoma, 8 cases of non-differentiated adenocarcinoma, 3 cases of mucinous adenocarcinoma, 1 cases of mastoid adenocarcinoma. The correlation of MR findings and dynamic contrast-enhanced MR Imaging△SI with MVD and expression of VEGF in hilar cholangiocarcinoma were analyzed.
Results (1)MR imaging findings: Hilar mass, dilatation of intrahepatic ducts and discontinuniy of hilar biliary ducts were seen in all cases, including 20 infiltrating, 7 exophytic and 1 intraluminal lesions. All the tumors were hypintense on T1-weighted spin-echo images. Most of the tumors presented iso- or mild hyper-intensity on T2-weighted images. According the different types of dynamic contrast-enhanced MR Imaging: 18 cases of I type、6 cases of II type、3 cases of III type and 1 cases of IV type. Spiral-like arteries were demonstrated in 4 cases and located strait in 2 cases on 3D-DCE-MRA during arterial phase. Portal vein was involved in 18 cases, presenting as infiltration, encasement or occlusion of the vein.
(2)MVD and VEGF expression detected by immunochemical methods: The MVD in tumor tissue and para-tumor tissue was significantly higher than in normal tissue(P<0.01).In 52 cases of normal tissues and tumor tissues, VEGF positive expression were found in 32 cases, and the mean MVD was 33.15±8.29; VEGF negative expression were found in 20 cases, and the mean MVD was 17.42±11.13. The difference between MVD、VEGF expression and histological type had no statistical significance (P>0.05).
(3)MVD in the groups of invasion and metastases in the lesions were higher than non-metastases (P<0.05); but their relation to the morphologic classification according to growth pattern were not significant (P>0.05) .There was correlation between MVD and dynamic enhancement pattern (P<0.05) ; the enhancement rate (△SI) of the early-phase signal intensity was significantly correlated with MVD and VEGF.
Conclusions (1)MR, including plain MR, MRCP , dynamic contrast-enhanced MRI and 3D-DCE-MRA ,can give more useful information about the diagnosis and preoperative evaluation in hilar cholangiocarcinoma.
(2)hilar cholangiocarcinoma progression was angiogenesis-correlation, and higher MVD and VEGF expression indicated poor prognosis.
(3)MR imaging findings and dynamic contrast-enhanced MR△SI is of potential value for estimating the degree of tumor angiogenesis, biologic behavior and prognosis of hilar cholangiocarcinoma. In some sense, MRI may estimate the degree of tumor angiogenesis, biologic behavior and prognosis of hilar cholangiocarcinoma.
引文
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