Glutamine Synthetase Immunostaining Correlates with Pathologic Features of Hepatocellular Carcinoma and Better Survival after Radiofrequency Thermal Ablation
Glutamine Synthetase Immunostaining Correlates with Pathologic Features of Hepatocellular Carcinoma and Better Survival after Radiofrequency Thermal Ablation
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DOI：
10.1158/1078-0432.ccr-09-1978
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发表时间：
2010-04-01
影响因子：
11.5
通讯作者：
Silini, Enrico M.
中科院分区：
文献类型：
--
作者：
Dal Bello, Barbara;Rosa, Laura;Silini, Enrico M.
目的：激活wnt通路识别具有特定流行病学和遗传特征的肝细胞癌（HCC）亚群。Wnt的激活可通过β -连环蛋白的突变和/或核易位以及谷氨酰胺合成酶（GS）的免疫反应性来预测。我们研究了GS染色是否与HCC的特定病理特征和射频热消融后的生存有关。实验设计：一所三级医院的单机构回顾性前瞻性研究。277例早期HCC肝硬化患者（平均年龄70岁，63%为男性，82.1%为丙型肝炎病毒阳性）连续接受射频热消融治疗。肿瘤平均大小2.7 cm；多发结节占20.3%；中位随访时间为36个月，总死亡率为54.6%。肿瘤样本主要通过活检获得（92.5%），并通过H&E和免疫染色检测β -连环蛋白和GS。通过Kaplan-Meier分析和Cox比例风险模型校正竞争风险，主要结局指标为总体死亡率和肿瘤特异性死亡率。结果：91例（43.9%）患者免疫染色呈gs阳性。这些肿瘤具有较大的体积（P = 0.012）和特征性的组织学特征（低分级、假腺泡、积水改变、胆汁染色、缺乏脂肪变性和纤维化）。其他临床或治疗变量在两组之间相似。通过单变量分析，与肿瘤特异性和总死亡率相关的变量是肿瘤复发、疾病进展、治疗后甲胎蛋白水平和GS染色。gs阳性患者的年总死亡率较低（12.4% vs 20%; P = 0.006）。通过多因素分析，GS免疫染色与降低的特异性死亡率（风险比0.58,95%可信区间0.34-0.97）和总死亡率（风险比0.62,95%可信区间0.40-0.96）相关。结论：标准组织学和GS状态确定HCC亚群具有独特的临床和病理特征。临床癌症研究；16 (7);2157 - 66。AACR (C) 2010。
Purpose: Activation of the wnt pathway identifies a subgroup of hepatocellular carcinomas (HCC) with specific epidemiologic and genetic profiles. Wnt activation is predicted by mutation and/or nuclear translocation of beta-catenin and by glutamine synthetase (GS) immunoreactivity. We investigated whether GS staining associates with specific pathologic features of HCC and with survival after radiofrequency thermal ablation.Experimental Design: Monoistitutional retrospective-prospective study in a tertiary hospital setting. Two hundred and seven cirrhotics (mean age, 70 years; 63% males, 82.1% hepatitis C virus positive) with early HCC were consecutively treated with radiofrequency thermal ablation (RFTA). Mean tumor size was 2.7 cm; 20.3% of patients had multiple nodules; and median follow-up was 36 months with 54.6% overall mortality. Tumor samples were mainly obtained by biopsy (92,5%) and examined by H&E and immunostaining for beta-catenin and GS. Main outcome measures were overall and tumor-specific mortality by Kaplan-Meier analysis and Cox proportional hazard models corrected for competing risks.Results: Ninety-one patients (43.9%) had GS-positive HCCs by immunostaining. These tumors had larger size (P = 0.012) and characteristic histology (low grade, pseudoacini, hydropic changes, bile staining, lack of steatosis, and fibrosis). Other clinical or treatment variables were similar between groups. Variables correlating with tumor-specific and overall mortality by univariate analysis were tumor recurrence, advanced disease, posttreatment alpha-fetoprotein levels, and GS staining. Yearly, overall mortality rate was lower in GS-positive patients (12.4 versus 20% yearly; P = 0.006). By multivariate analysis, GS immunostaining correlated with reduced specific (hazard ratio, 0.58; 95% confidence interval, 0.34-0.97) and overall mortality (hazard ratio, 0.62; 95% confidence interval, 0.40-0.96).Conclusions: Standard histology and GS status identify a HCC subset with distinct clinical and pathologic features. Clin Cancer Res; 16(7); 2157-66. (C)2010 AACR.