HIF-1α和E-cadherin在原发性肝细胞癌中的表达及意义
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摘要
目的:本实验运用免疫组织化学方法在42例原发性肝细胞癌手术切除标本中检测缺氧诱导因子-1a及上皮性钙粘素的表达,探讨在原发性肝细胞癌中两者的关系,以完善钙粘素的调节机制及缺氧诱导因子—1a在肿瘤转移中的作用,为以后的研究及治疗提供依据。
材料与方法:收集原发性肝细胞癌患者手术后病理石蜡标本42例作为实验组,收集同一时间段内8例病理证实为正常肝脏组织的石蜡包埋组织块作为对照组。采用免疫组织化学SABC法染色。检测所用一抗为兔抗人HIF-1a及E—cadherin蛋白抗体。免疫组化染色结果运用病理图像自动分析仪进行分析,比较各切片平均光密度值,检测缺氧诱导因子-1a及上皮性钙粘素在原发性肝癌组织和正常肝脏组织中的表达水平。统计学分析采用SPSS13.0统计软件对数据进行处理,两个变量各组间均数比较采用成组设计的方差分析One-Way ANOVA检验,组间比较采用独立样本t检验,两变量间相关分析采用Pearson分析,以P＜0.05认为具有显著性差异。
结果:1、在8例正常肝脏组织染色HIF—1α的平均光密度值为0.03113±0.043888,E—cad的平均光密度值为0.476550±0.0817397,42例原发性肝细胞癌组织切片染色中,在21例高分化组织中HIF—1α的平均光密度值为0.184556±0.0864201,E—cad为0.311738±0.1132042,在21低分化组织中HIF—1α的平均光密度值0.287551±0.1373203,E—cad的平均光密度值为0.242618±0.0709841,肿瘤组之间及与对照组之间阳性表达差异有显著的统计学意义(P＜0.01)。2、在侵袭转移组的17例原发性肝细胞癌组织中HIF—1α的平均光密度值为0.294671±0.1275208,E—cad的平均光密度值为0.196853±0.0607084,非侵袭转移组25例原发性肝细胞癌组织染色HIF—1α的平均光密度值为0.196194±0.1079300,E—cad的平均光密度值为0.321248±0.1105315,侵袭转移组与非侵袭转移组之间阳性表达差异有显著的统计学意义(P＜0.05)。3、在PHCC组织中HIF—1α水平上调,E—cad表达水平均下调,对两者进行相关分析,在高分化非侵袭转移组13例组织中两者显著相关(P＜0.01),在高分化侵袭转移组8例组织中两者显著相关(P＜0.05),在低分化非侵袭转移组12例组织中两者无明显相关性P＞0.05),在低分化侵袭转移组9例组织中两者无明显相关性(P＞0.05)。
结论:HIF-1a在原发性肝细胞癌组织中的表达水平均明显上调,E—cadherin在原发性肝细胞癌组织中的表达水平均明显下调。在高分化组和低分化组及转移组和非转移组间皆有显著差异。二者在高分化肝细胞癌组织中的表达有显著相关性,在低分化的肝细胞癌中无明显相关性。缺氧诱导因子-1a及上皮性钙粘素在肝细胞癌组织中的异常表达提示缺氧诱导因子-1a可在高分化肿瘤中通过下调上皮性钙粘素水平,从而促进肿瘤细胞的转移。
Objective: To investigate the expression of HIF-1a and E-cadherin in primary hepatic cellular carcinoma(PHCC) tissues. Trough this experiment,we purpose to discuss its contribution in development of PHCC and raise morphology foundation for clinical study of PHCC.
Methods: primary hepatic cellular carcinoma(PHCC) specimens were procured from 42 patients,with 8 cases of normal liver tissue being control group. HIF-1a and E - cadherin levels were assessed by immunohistochemical method. On the other hand,we analyzed the image by mean optical density.
Result: The level of positive HIF-1αimmunostaining in PHCC is higher than in nomal liver tissue (P<0.01), and The level of positive E—cadherin immunostaining in PHCC is lower than in nomal liver tissue (P<0.05). We could find the expression of HIF-1a has relation with the expression of E-cadherin in PHCC with high differentiation (P<0.01) , but not in low differentiation group.
Conclusions: The level of positive HIF-1aimmunostaining in PHCC is higher than in nomal liver tissue. The level of positive E—cadherin immunostaining in PHCC is lower than in nomal liver tissue HIF-1 alpha might repress E-cadherin expression asscociated with development of PHCC with high differentiation and increase the metastasizing ability of PHCC.
材料与方法:收集原发性肝细胞癌患者手术后病理石蜡标本42例作为实验组,收集同一时间段内8例病理证实为正常肝脏组织的石蜡包埋组织块作为对照组。采用免疫组织化学SABC法染色。检测所用一抗为兔抗人HIF-1a及E—cadherin蛋白抗体。免疫组化染色结果运用病理图像自动分析仪进行分析,比较各切片平均光密度值,检测缺氧诱导因子-1a及上皮性钙粘素在原发性肝癌组织和正常肝脏组织中的表达水平。统计学分析采用SPSS13.0统计软件对数据进行处理,两个变量各组间均数比较采用成组设计的方差分析One-Way ANOVA检验,组间比较采用独立样本t检验,两变量间相关分析采用Pearson分析,以P＜0.05认为具有显著性差异。
结果:1、在8例正常肝脏组织染色HIF—1α的平均光密度值为0.03113±0.043888,E—cad的平均光密度值为0.476550±0.0817397,42例原发性肝细胞癌组织切片染色中,在21例高分化组织中HIF—1α的平均光密度值为0.184556±0.0864201,E—cad为0.311738±0.1132042,在21低分化组织中HIF—1α的平均光密度值0.287551±0.1373203,E—cad的平均光密度值为0.242618±0.0709841,肿瘤组之间及与对照组之间阳性表达差异有显著的统计学意义(P＜0.01)。2、在侵袭转移组的17例原发性肝细胞癌组织中HIF—1α的平均光密度值为0.294671±0.1275208,E—cad的平均光密度值为0.196853±0.0607084,非侵袭转移组25例原发性肝细胞癌组织染色HIF—1α的平均光密度值为0.196194±0.1079300,E—cad的平均光密度值为0.321248±0.1105315,侵袭转移组与非侵袭转移组之间阳性表达差异有显著的统计学意义(P＜0.05)。3、在PHCC组织中HIF—1α水平上调,E—cad表达水平均下调,对两者进行相关分析,在高分化非侵袭转移组13例组织中两者显著相关(P＜0.01),在高分化侵袭转移组8例组织中两者显著相关(P＜0.05),在低分化非侵袭转移组12例组织中两者无明显相关性P＞0.05),在低分化侵袭转移组9例组织中两者无明显相关性(P＞0.05)。
结论:HIF-1a在原发性肝细胞癌组织中的表达水平均明显上调,E—cadherin在原发性肝细胞癌组织中的表达水平均明显下调。在高分化组和低分化组及转移组和非转移组间皆有显著差异。二者在高分化肝细胞癌组织中的表达有显著相关性,在低分化的肝细胞癌中无明显相关性。缺氧诱导因子-1a及上皮性钙粘素在肝细胞癌组织中的异常表达提示缺氧诱导因子-1a可在高分化肿瘤中通过下调上皮性钙粘素水平,从而促进肿瘤细胞的转移。
Objective: To investigate the expression of HIF-1a and E-cadherin in primary hepatic cellular carcinoma(PHCC) tissues. Trough this experiment,we purpose to discuss its contribution in development of PHCC and raise morphology foundation for clinical study of PHCC.
Methods: primary hepatic cellular carcinoma(PHCC) specimens were procured from 42 patients,with 8 cases of normal liver tissue being control group. HIF-1a and E - cadherin levels were assessed by immunohistochemical method. On the other hand,we analyzed the image by mean optical density.
Result: The level of positive HIF-1αimmunostaining in PHCC is higher than in nomal liver tissue (P<0.01), and The level of positive E—cadherin immunostaining in PHCC is lower than in nomal liver tissue (P<0.05). We could find the expression of HIF-1a has relation with the expression of E-cadherin in PHCC with high differentiation (P<0.01) , but not in low differentiation group.
Conclusions: The level of positive HIF-1aimmunostaining in PHCC is higher than in nomal liver tissue. The level of positive E—cadherin immunostaining in PHCC is lower than in nomal liver tissue HIF-1 alpha might repress E-cadherin expression asscociated with development of PHCC with high differentiation and increase the metastasizing ability of PHCC.
引文
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