【作者】 李清国；

【导师】 赵广法； 师英强； 傅红；

【作者基本信息】 复旦大学 ， 肿瘤学， 2008， 硕士

【摘要】 研究目的:研究C-erbB-2和VEGF在大肠癌肝转移灶和原发灶中的表达情况,分析两者在肝转移灶和大肠癌原发灶中表达是否存在差异,探讨其表达的规律性,分析其阳性表达与临床病理特征以及预后的关系。材料与方法:收集2000～2007年间复旦大学肿瘤医院外科手术切除的44例大肠癌肝转移患者的临床病理资料和蜡块标本,对所有入组病例进行随访。运用免疫组化Envision两步法检测C-erbB-2和VEGF在大肠癌肝转移灶、原发灶中的表达情况,并分别取15例正常大肠组织和肝脏切缘组织作对照,分析两者在肝转移灶和大肠癌原发灶中表达是否存在差异,探讨两者表达的规律性,分析其阳性表达与临床病理特征以及预后的关系。研究结果:1.C-erbB-2在大肠癌肝转移灶、肝脏切缘组织、大肠癌原发灶、正常大肠组织中的阳性率分别为38.64%、20.00%、31.25%、0,C-erbB-2在大肠癌中的阳性率显著高于正常大肠组织(P＜0.05),其在肝转移灶和肝脏切缘组织中的阳性率无显著统计学差异(P＞0.05)。VEGF在大肠癌肝转移灶、肝脏切缘组织、大肠癌原发灶、正常大肠组织中的阳性率分别为52.27%、40.00%、40.63%、0%,VEGF在大肠癌中的阳性率显著高于正常大肠组织(P＜0.05),而其在肝转移灶和肝脏切缘组织中的表达水平无显著差异(P＞0.05)2.C-erbB-2和VEGF在大肠癌肝转移灶和原发灶中表达水平没有显著统计学差异(P＞0.05)。3.C-erbB-2和VEGF两者在大肠癌肝转移灶和原发灶中的表达没有显著相关性(P＞0.05)。4.VEGF在大肠癌肝转移灶和原发灶中表达存在一致性(P＜0.05),而c-erbB-2则没有一致性(P＞0.05)。5.C-erbB-2阳性表达和肝转移灶数目和分布相关(P＜0.05),c-erbB-2阳性表达的患者和阴性表达的患者术后长期生存率没有显著差异(P＞0.05);VEGF的阳性率和肝转移灶的大小密切相关性(P＜0.05),VEGF阳性表达的患者肝转移灶切除术后长期生存率要低于VEGF无表达的患者(P＜0.05);C-erbB-2和VEGF联合检测可更有助于预后判断。6.C-erbB-2在大肠癌肝转移灶和原发灶中的强阳性(++和+++)率较低,分别为11.36%(5/44)和9.73%(3/32),且C-erbB-2主要为胞浆阳性。7.肝转移灶切缘处的肝组织中c-erbB-2和VEGF也有较高的表达水平,一部分患者肝转移灶切缘处的肝组织表达强度高于肿瘤组织。8.单因素分析显示VEGF表达水平是预后的重要影响因素之一(P＜0.05),多因素分析显示VEGF并不是预后的一个独立影响因素(P＞0.05),而C-erbB-2阳性表达和预后没有显著相关性(P＞0.05)。结论:1.C-erbB-2和VEGF广泛表达于大肠癌肝转移灶和原发灶中,在肝脏切缘组织中两者也有较高表达,而在正常大肠组织中两者无表达。2.C-erbB-2和VEGF在肝转移灶和原发灶中表达水平没有显著差异。3.C-erbB-2和VEGF两者在大肠癌肝转移灶和原发灶中表达没有显著相关性。4.VEGF在大肠癌肝转移灶中和原发灶中表达存在一致性,可以通过原发灶中VEGF的检测初步了解转移灶的表达情况,而c-erbB-2则在肝转移灶和原发灶中表达没有一致性。5.C-erbB-2阳性表达和肝转移灶数目和分布相关,对预后没有判断价值;VEGF的阳性率和肝转移灶的大小密切相关性,阳性表达的患者肝转移灶术后长期生存率要低于VEGF无表达的患者;C-erbB-2和VEGF联合检测可更有助于预后判断。6.C-erbB-2在大肠癌肝转移灶和原发灶中的强阳性率较低,且C-erbB-2主要为胞浆阳性。更多还原

【Abstract】 Objective:To investigate the expression of c-erbB-2 and VEGF protein expression in liver metastases and its corresponding primary colorectal cancer,to probe whether there are any regularity of its express in liver metastases and its primary cancer and to analyze whether there are any relationships of their expressions with clinicopathologic characteristics.Also we make a survival analysis to know what make a negative affect on survival after hepatectomy of liver metastases.Methods:Forty-four patients operated between 2000 and 2007 in Shanghai Cancer Hospital for colorectal cancer liver metastases were included.Clinicopathologic data were obtained from the patients’ records.Immunohistological EnVision staining was used to detect the expression of c-erbB-2 and VEGF in Forty-four formalin-fixed liver metastases and thirty-two primary colorectal tumors,and 15 cases of normal colorectal tissues and liver tissues at surgical margin were taken as control research respectively. SPSS13.0 was used to analyze the correlation between c-erbB-2 and VEGF expression and clinical pathological parameters,to probe whether there are any correlation and conformity between c-erbB-2 and VEGF expression in liver metastases and its primary.Results:1.The positive percentages of c-erbB-2 in liver metastases、liver paracancerous tissues、colorectal cancer、normal colorectal tissues were 38.64%、20.00%、31.25%、0.The c-erbB-2 expression levels were significance higher in colorectal cancer than its normal tissues(P＜0.05),but their difference were not observe between liver metastases and its paracancerous tissues(P＞0.05).The positive percentages of VEGF were52.27%、40.00%、40.63%、0%in liver metastases、liver paracancerous tissues、colorectal cancer、normal colorectal tissues.The VEGF were significance higher in colorectal cancer than its normal tissues (P＜0.05),but no difference were observe between liver metastases and its paracancerous tissues(P＞0.05).2.There is no significance different of c-erbB-2 and VEGF expression between liver metastases and primary cancer(P＞0.05).3.There is no significance correlation between c-erbB-2 and VEGF expression in liver metastases and primary cancer(P＞0.05).4.There is conformity of VEGF expression between liver metastases and its primary(P＜0.05),but not c-erbB-2(P＞0.05).5.The expression of c-erbB-2 was positively correlated with distributes and numbers of liver metastases(P＜0.05),but have no relationship with overall survival after hepatectomy of liver metastases(P＞0.05),VEGF expression was association with maximal diameter of liver metastases and poor survival (P＜0.05).Combine analyses of c-erbB-2 and VEGF may show better predictive role after resection of liver metastases.6.There is low strongly positive expression(++ and +++) of c-erbB-2 at liver metastases and colorectal cancer,which are 11.36%(5/44) and 9.73%(3/32) respectively,and mainly is cytoplasm positive.7.There is also overexpression of c-erbB-2 and VEGF at liver resection margin tissues,and sometimes there are higher expressions of VEGF at paracancerous tissues than tumor itself.8.Log rank test shows factors that VEGF expression have significance impact on overall survival after resection of liver metastases(P＜0.05),but Cox regression analyses didn’t show it is an independent factors of survival(P＞0.05).Conclusion:1.C-erbB-2 and VEGF is common expressed in liver metastases and its primary cancer,c-erbB-2 and VEGF also are higher expression in liver resection margin tissuses,but not normal colorectal tissues.2.There is no significance different between c-erbB-2 and VEGF expression in liver metastases and primary cancer.3.There are no significance correlation between c-erbB-2 and VEGF expression in liver metastases and its primary cancer. 4.There is conformity of VEGF expression between liver metastases and its primary, we can roughly understand the liver expression of VEGF by check its primary colorectal cancer,but it is not the same of c-erbB-2.5.C-erbB-2 expression was positively correlated with distributes and numbers of liver metastases,but have no relationship with overall survival after hepatectomy of liver metastases,VEGF expression was association with maximal diameter of liver metastases and poor survival.Combine analyses of c-erbB-2 and VEGF may show better predictive role after resection of liver metastases.6.C-erbB-2 is mainly cytoplasm positive with low strongly positive.更多还原