论文标题:CD105的表达与肝细胞癌术后复发转移的关系
The Association between CD105 Expression and Postoperative Recurrence and Metastasis of Hepatocellular Carcinoma
论文作者 鲁伟群
论文导师 杨连粤,论文学位 硕士,论文专业 外科学
论文单位 中南大学,点击次数 57,论文页数 51页File Size2467k
2003-05-01论文网 http://www.lw23.com/lunwen_119030702/ 肝细胞癌;CD105;CD34;微血管密度;复发和转移
hepatocellular carcinoma,CD 105,CD34,micro-vessel density;recurrence and metastasis
目的：通过研究CD105和CD34在肝细胞癌(hepatocellular carcinoma，HCC)的微血管上的表达与HCC术后复发转移的关系来寻找准确判断HCC患者预后的标志物。并探讨孤立性大肝癌的某些特殊分子病理特征及其生物学行为。 方法：对113例HCC组织及其相应癌旁肝组织和14例正常肝组织标本用免疫组织化学方法检测CD105、CD34和VEGF的表达；对CD105、CD34阳性血管进行MVD计数，对VEGF进行半定量计数，并结合临床病理特征和随访结果进行分析。 结果：CD105和CD34在HCC组织中均呈弥漫性棕黄色至棕褐色窦隙状阳性表达(100％，113／113)；CD105在癌旁肝组织(100％，113／113)和正常肝组织(100％，14／14)中均呈阴性表达；而CD34在癌旁肝组织(106／113，93.8％)和正常肝组织(86.7％，12／14)中仍可见阳性表达。HCC组织中抗CD105抗体评价的MVD(micro-vessel density evaluated by anti-CD105 antibody，CD105-MVD)和抗CD34抗体评价的MVD(micro-vessel density evaluated by anti-CD34 antibody，CD34-MVD)分别为71.7±8.3和106.3±10.4，两者呈正相关(r=0.248，P=0.021)。CD34-MVD与VEGF的表达正相关(r=0.243，P=0.024)，而CD105-MVD也与VEGF的表达相关(r=0.300，P=0.005)。被抗CD34抗体标记而不被抗CD105抗体标记的微血管与VEGF的表达不相关(r=0.111，P=0.311)。CD105-MVD与HCC发生镜下静脉浸润密切相关(r_s=0.254，P=0.018)，而与肝硬化程度、肿瘤直径、包膜形成、Edmondson"s分级、术前AFP浓度无相关关系；CD34-MVD与上述各临床病理指标的相关性均未达到统计学显著性意义。全部HCC患者的2年生存率为30.1％，低CD105-MVD组HCC患者的2年生存率为47.1％，而高CD105-MVD组HCC患者的2年生存率为13.5％，二者差异具有统计学显著性意义(P=0.026)。而低CD34-MVD组HCC患者的2年生存率与高CD34-MVD组HCC患者的2年生存率分别为33.3％和26.9％，差别无显著性意义(P=0.601)。发生镜下静脉浸润的HCC患者的2年生存率为14.8％，而未发生镜下静脉浸润的HCC患者的2年生存率为46.9％，二者差异具有统计学显著性意义(P=0.031)；未发现其它病理特征对HCC患者的2年生存率的影响达到统计学显著性意义。与结节性肝癌相比，孤立性大肝癌的细胞分化程度较高、更易形成包膜、发生镜下静脉浸润较少、伴随肝硬化程度较轻。孤立性大肝癌的n105啪D与结节性肝癌的 CD105－MVD分别为 60．42上10．55和 82．58士6．41，差异具有统计学显著性意义（P二0．02），而与小肝癌的CD105－MVD（54．88土8．sl）的差异则无显著意义u司．352人 孤立性大肝癌患者的2年生存率65．0划与小肝癌患者的2年生存率格2．2们的差别无统计学显著性意义护和．584厂 且均高于结节性肝癌患者的2年生存率门3．3们。各类型肝癌中，高CD105啪VD组HCC患者的2年生存率均低于低CD105喇VD组mC患者的2年生存率，且差异均具有统计学显著性意义；而高CD34－MVD组mC患者的2年生存率与低CD34－MVD乡HCC患者的2年生存率的差异均未达到统计学显著性意义；镜下静脉浸润对小肝癌和孤立性大肝癌患者的2年生存率的影响均具有统计学显著性意义护对．025和 P司．019＼对结节性肝癌患者的 2年生存率的影响未达统计学显著性意义呼叫．912）；也未发现其它病理特征对各类HCC患者的2年生存率的影响达到统计学显著性意义。全部HCC患者、小肝癌患者、孤立性大肝癌患者的多因素分析均表明，CD 05仇VD为影响预后的独立因素。 结论：抗CD 105抗体能较抗CD34抗体更特异地标记HCC新生血管；CD 05MVD较CD34MVD有更准确更客观地反映HCC组织的MVD；CD105仇VD可作为判断肝癌患者预后的一个有效指标；HCC诱导新生血管形成的能力可能与孤立性大肝癌患者的预后有关。
Objective: To find valid prognostic marker for hepatocellular carcinoma (HHC) patients through studying the correlation between CD 105 or CD34 expression and postoperative recurrence and metastasis as well as to explore some special molecular pathological features and biological behavior of solitary large HCC.Methods: 113 HCC cases with paracarcinomatous tissue and 14 normal liver tissue specimen were stained with CD 105, CD34, VEGF by immunohistochemistry method. Quantitation of micro-vessels which was highlighted by anti-CD 105 mAb and anti-CD34 mAb and semi-quantitation of VEGF expression was performed and analyzed in conjunction with the clinical-pathological characteristics and the result of follow-up.Results: Negative expression of CD 105 on vascular endothelial in normal liver tissue (100%, 14/14) and paracarcinomatous liver tissue (100%, 113/113) was found, while the expression on vascular endothelial in HCC tissue were positive (100%, 113/113). CD34 expression, on the other hand, was found positively in normal liver tissue (86.7%, 12/14) and paracarcinomatous liver tissue (93.8%, 106/113) as well as in HCC tissue (100%, 113/113). The micro-vessel density evaluated by an anti-CD 105 monoclonal antibody (CD105-MVD) and an anti-CD34 monoclonal antibody (CD34-MVD) were 71.7?8.3 and 106.3?10.4, respectively. There was statistically significant correlation between CD105-MVD and CD34-MVD (r=0.248,P = 0.021). CD34-MVD was significantly correlated with VEGF expression (r=0.243,P=0.024), while CD105-MVD was more closely correlated with VEGF expression (r= 0.300, P=0.005)o There proved to be no correlation between VEGF expression and micro-vessels that were highlighted by anti-CD34 mAb and were not highlighted by anti-CD 105 mAb. The correlation between CD105-MVD values and microscopic venous invasion were statistically significant (r=0.254, P=0.018), while we didn"t find any significant correlation between CD15-MVD and liver cirrhosis, tumor diameter,incapsule formation, Edmondson"s grade , preoperative alpha-fetoprotein (AFP) concentration .There was no significant correlation between CD34-MVD and any such clinical-pathological features. The 2-year survival rate of all HCC patients was 30.1%. The 2-year survival rate of lower CD105-MVD (CD105-MVD<56, the median values) HCC patients was 47.1%, significantly higher than that of higher CD105-MVD HCC patients (13.5%, P=0.014). Whereaas the 2-year survival rate of lower CD34-MVD (CD105-MVD<94, 33.3%) HCC patients also seemed to be higher than that of higher CD34-MVD HCC patients (26.9%), the difference did not reach a statistical significance (P=0.601). The 2-year survival rate of HCC patients whose specimen had been found microscopic venous invasion was 14.8%, significantly lower than that of HCC patients whose specimen hadn"t (46.9%, P=0.031), while we could not find any other clinical-pathological characteristics involved in this study influent the 2-year survival rate of HCC patients significantly. When compared to nodular HCC, cell differentiation was better, capsule formation was more easily, microscopic venous invasion occurred less frequently, associated liver cirrhosis was milder in solitary large HCC. The CD105-MVD in solitary large HCC and in nodular HCC were 60.42?10.55 and 82.58?6.41, respectively, and the difference between them was significant (P=0.021), while the difference between CD105-MVD in solitary large HCC and in small HCC (54.88?8.81) was not (P=0.352). The 2-year survival in solitary large HCC patients (55.0%) and small HCC patients (52.2%) were all higher than that of nodular HCC (13.3%), and the difference between solitary large HCC and small HCC didn"t reach a statistical significance (P=0.584). CD105-MVD, but not CD34-MVD, could significantly influent the 2-year survival rate of HCC patients in each groups. Microscopic venous invasion could significantly influent the 2-year survival rate of small HCC patients and solitary large HCC patients (P=0.025 and P=0.019, respectively) except nodular HCC patients (P=0.912), while we
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