Objective and background： Although p21 ras has been reported to be upregulated in hepatocellular carcinoma complicating chronic hepatitis C type I, p21 ras has a different role in advanced stages, as it has been foun...Objective and background： Although p21 ras has been reported to be upregulated in hepatocellular carcinoma complicating chronic hepatitis C type I, p21 ras has a different role in advanced stages, as it has been found to be downregulated. The goal of this study was to investigate the status of p21 ras in early-stage/low-grade and late-stage/high-grade hepatocellular carcinoma and its possible link to apoptosis. Material and methods： Thirty-five cases each of chronic HCV hepatitis type 4 （group I） and cirrhosis with hepatocellular carcinoma （HCC） complicating chronic HCV hepatitis （groups Ⅱ and Ⅲ） were immunohistochemically evaluated using a p21 ras polyclonal antibody. The apoptotic index was determined in histologic sections using the terminal deoxynncleotidyl transferase-mediated d-UTP biotin nick end labeling （TUNEL） assay. Results： Significant differences （P=0.001） were detected in p21 ras protein expression between the three groups. A near 2-fold increase in p21 ras staining was observed in the cirrhotic cases compared to the hepatitis cases, and p21 ras expression was decreased in the HCC group, p21 ras expression correlated with stage （r=0.64, P--0.001） and grade （r=-0.65, P=0.001） in the HCC group and grade in the HCV group （r=0.44, P=0.008）. Both p21 ras expression and TUNEL-LI were significantly lower in large HCCs compared to small HCCs （P=0.01 each）. The TUNEL values were negatively correlated with stage in the HCC group （r=-0.85, P=0.001）. The TUNEL values were also negatively correlated with grade in both the HCV and HCC groups （r=0.89, P=0.001 and r=0.53, P=0.001, respectively）. The p21 ras scores were significantly correlated with the TUNEL-LI values in the HCC group （r=0.63, P=0.001） and HCV group （r=0.88, P=0.001）. Conclusions： p21 ras acts as an initiator in HCC complicating type 4 chronic HCV and is downregulated with HCC progression, which most likely promotes tumor cell survival because it facilitates the downregulation of apoptosis with tumor progression.展开更多
目的探讨P21Ras和细胞外信号调节激酶(P-ERK)在子宫内膜癌中的表达及其介导的丝裂原活化蛋白激酶(mitogen activated protein kinase,Ras-Raf-MEK-ERK)途径与子宫内膜癌发生发展之间的关系。方法采用免疫组织化学SP法对49例子宫内膜癌...目的探讨P21Ras和细胞外信号调节激酶(P-ERK)在子宫内膜癌中的表达及其介导的丝裂原活化蛋白激酶(mitogen activated protein kinase,Ras-Raf-MEK-ERK)途径与子宫内膜癌发生发展之间的关系。方法采用免疫组织化学SP法对49例子宫内膜癌和20例子宫内膜非典型增生,12例增生期内膜组织中P21Ras和P-ERK的表达进行检测,分析两者的表达与子宫内膜癌患者临床病理特征之间的关系。结果P21Ras和P-ERK在子宫内膜癌中的表达率分别为75.51%(37/49)、71.43%(35/49),明显高于非典型增生内膜35.00%(7/20)、40.00%(8/20)及增生期子宫内膜0(0/12)、8.33%(1/12)(P<0.05)。P21ras和P-ERK在高中分化子宫内膜癌中的表达率63.64%(21/33)、60.61%(20/33),显著低于低分化子宫内膜癌100%(16/16)、93.75%(15/16)(P<0.05)。P-ERK在手术病理分期中Ⅲ的表达率为100%,明显高于Ⅰ期58.62%(17/29)、Ⅱ期85.71%(12/14)。此外,P-ERK的表达与肌层浸润深度有关,在<1/2肌层深度中的表达53.85%(14/26)明显小于≥1/2肌层深度的表达91.30%(21/23)(P<0.05)。P21Ras和P-ERK的表达呈正相关(rs=0.480,P<0.01)。结论P21Ras和P-ERK与子宫内膜癌的发生和发展有关,且两者存在协同作用;②Ras-MAPK途径的异常活化与子宫内膜癌的发生密切相关。展开更多
文摘Objective and background： Although p21 ras has been reported to be upregulated in hepatocellular carcinoma complicating chronic hepatitis C type I, p21 ras has a different role in advanced stages, as it has been found to be downregulated. The goal of this study was to investigate the status of p21 ras in early-stage/low-grade and late-stage/high-grade hepatocellular carcinoma and its possible link to apoptosis. Material and methods： Thirty-five cases each of chronic HCV hepatitis type 4 （group I） and cirrhosis with hepatocellular carcinoma （HCC） complicating chronic HCV hepatitis （groups Ⅱ and Ⅲ） were immunohistochemically evaluated using a p21 ras polyclonal antibody. The apoptotic index was determined in histologic sections using the terminal deoxynncleotidyl transferase-mediated d-UTP biotin nick end labeling （TUNEL） assay. Results： Significant differences （P=0.001） were detected in p21 ras protein expression between the three groups. A near 2-fold increase in p21 ras staining was observed in the cirrhotic cases compared to the hepatitis cases, and p21 ras expression was decreased in the HCC group, p21 ras expression correlated with stage （r=0.64, P--0.001） and grade （r=-0.65, P=0.001） in the HCC group and grade in the HCV group （r=0.44, P=0.008）. Both p21 ras expression and TUNEL-LI were significantly lower in large HCCs compared to small HCCs （P=0.01 each）. The TUNEL values were negatively correlated with stage in the HCC group （r=-0.85, P=0.001）. The TUNEL values were also negatively correlated with grade in both the HCV and HCC groups （r=0.89, P=0.001 and r=0.53, P=0.001, respectively）. The p21 ras scores were significantly correlated with the TUNEL-LI values in the HCC group （r=0.63, P=0.001） and HCV group （r=0.88, P=0.001）. Conclusions： p21 ras acts as an initiator in HCC complicating type 4 chronic HCV and is downregulated with HCC progression, which most likely promotes tumor cell survival because it facilitates the downregulation of apoptosis with tumor progression.
文摘目的探讨P21Ras和细胞外信号调节激酶(P-ERK)在子宫内膜癌中的表达及其介导的丝裂原活化蛋白激酶(mitogen activated protein kinase,Ras-Raf-MEK-ERK)途径与子宫内膜癌发生发展之间的关系。方法采用免疫组织化学SP法对49例子宫内膜癌和20例子宫内膜非典型增生,12例增生期内膜组织中P21Ras和P-ERK的表达进行检测,分析两者的表达与子宫内膜癌患者临床病理特征之间的关系。结果P21Ras和P-ERK在子宫内膜癌中的表达率分别为75.51%(37/49)、71.43%(35/49),明显高于非典型增生内膜35.00%(7/20)、40.00%(8/20)及增生期子宫内膜0(0/12)、8.33%(1/12)(P<0.05)。P21ras和P-ERK在高中分化子宫内膜癌中的表达率63.64%(21/33)、60.61%(20/33),显著低于低分化子宫内膜癌100%(16/16)、93.75%(15/16)(P<0.05)。P-ERK在手术病理分期中Ⅲ的表达率为100%,明显高于Ⅰ期58.62%(17/29)、Ⅱ期85.71%(12/14)。此外,P-ERK的表达与肌层浸润深度有关,在<1/2肌层深度中的表达53.85%(14/26)明显小于≥1/2肌层深度的表达91.30%(21/23)(P<0.05)。P21Ras和P-ERK的表达呈正相关(rs=0.480,P<0.01)。结论P21Ras和P-ERK与子宫内膜癌的发生和发展有关,且两者存在协同作用;②Ras-MAPK途径的异常活化与子宫内膜癌的发生密切相关。
