AIM: Expression of heat shock proteins (HSPs) is frequently up-regulated in hepatocellular carcinoma (HCC), which evolves from dysplastic nodule (DN) and early HCC to advanced HCC. However, little is known about the d...AIM: Expression of heat shock proteins (HSPs) is frequently up-regulated in hepatocellular carcinoma (HCC), which evolves from dysplastic nodule (DN) and early HCC to advanced HCC. However, little is known about the differential expression of HSPs in multistep hepatocarcinogenesis. It was the purpose of this study to monitor the expression of HSPs in multistep hepatocarcinogenesis and to evaluate their prognostic significance in hepatitis B virus (HBV)related HCC.METHODS: Thirty-eight HCC and 19 DN samples were obtained from 52 hepatitis B surface antigen-positive Korean patients. Immunohistochemical and dot immunoblot analyses of HSP27, HSP60, HSP70, HSP90, glucoseregulated protein (GRP)78, and GRP94 were performed and their expression at different stages of HCC development was statistically analyzed.RESULTS: Expression of HSP27, HSP70, HSP90, GRP78, and GRP94 increased along with the stepwise progression of hepatocarcinogenesis. Strong correlation was found only in GRP78 (Spearman's r= 0.802). There was a positive correlation between the expressions of GRP78, GRP94, HSP90, or HSP70 and prognostic factors of HCC. Specifically, the expression of GRP78, GRP94, or HSP90 was associated significantly with vascular invasion and intrahepatic metastasis.CONCLUSION: The expressions of HSPs are commonly up-regulated in HBV-related HCCs and GRP78 might play an important role in the stepwise progression of HBVrelated hepatocarcinogenesis. GRP78, GRP94, and HSP90 may be important prognostic markers of HBV-related HCC, strongly suggesting vascular invasion and intrahepatic metastasis.展开更多
AIM: To design a classification tool for the histological assessment of hepatocellular carcinoma (HCC), dysplastic nodules (DN), and macroregenerative nodules (MRN) in cirrhotic liver.METHODS: Two hundred and twelve h...AIM: To design a classification tool for the histological assessment of hepatocellular carcinoma (HCC), dysplastic nodules (DN), and macroregenerative nodules (MRN) in cirrhotic liver.METHODS: Two hundred and twelve hepatocellular nodules (106 HCC;74 MRN;32 DN) were assessed systematically, quantitatively, and semiquantitatively as appropriate for 10 histological features that have been described as helpful in distinguishing small HCC, DN, and MRN in cirrhotic livers. The data were analyzed by multiple correspondence analysis (MCA).RESULTS: MCA distributed HCC, DN, and MRN as defined by traditional histological evaluation as well as the individual histological variables, in a 'malignancy scale'.Based on the MCA data representation, we created a classification tool, which categorizes an individual nodular lesion as MRN, DN, or HCC based on the balance of all histological features (i.e., vascular invasion, capsular invasion, tumor necrosis, tumor heterogeneity, reticulin loss,capillarization of sinusoids, trabecular thickness, nuclear atypia, and mitotic activity). The classification tool dassified most (83%) of a validation set of 47 nodules in the same way as the routine histological assessment. No discrepandes were present for DN and MRN between the routine histological assignment and the classification tool. Of 25 HCC assigned by routine assessment in the validation set, 8were assigned to the DN category by the classification tool.CONCLUSION: We have designed a classification tool for the histological assessment of HCC and its putative precursors in cirrhotic liver. Application of this tool systematically records histological features of diagnostic importance in the evaluation of small HCC.展开更多
AIM:To elucidate the variety of ways early-stage hepatocellular carcinoma(HCC)can appear on magnetic resonance(MR)imaging by analyzing T1-weighted,T2-weighted,and gadolinium-enhanced dynamic studies.METHODS:Seventy-th...AIM:To elucidate the variety of ways early-stage hepatocellular carcinoma(HCC)can appear on magnetic resonance(MR)imaging by analyzing T1-weighted,T2-weighted,and gadolinium-enhanced dynamic studies.METHODS:Seventy-three patients with well-differentiated HCC(wHCC)or dysplastic nodules were retrospectively identified from medical records,and new histological sections were prepared and reviewed.The tumor nodules were categorized into three groups:dysplastic nodule(DN),wHCC compatible with Edmondson-Steiner grade I HCC(w1-HCC),and wHCC compatible with Edmondson-Steiner gradeⅡHCC(w2-HCC).The signal intensity on pre-contrast MR imaging and the enhancing pattern for each tumor were recorded and compared between the three tumor groups.RESULTS:Among the 73 patients,14 were diagnosed as having DN,40 were diagnosed as having w1-HCC,and 19 were diagnosed as having w2-HCC.Hyperintensity measurements on T2-weighted axial images(T2WI)were statistically significant between DNs and wHCC(P=0.006)and between DN and w1-HCC(P=0.02).The other imaging features revealed no significant differences between DN and wHCC or between DN and w1-HCC.Hyperintensity on both T1W out-phase imaging(P=0.007)and arterial enhancement on dynamic study(P=0.005)showed statistically significant differences between w1-HCC and w2-HCC.The other imaging features revealed no significant differences between w1-HCC and w2-HCC.CONCLUSION:In the follow-up for a cirrhotic nodule,increased signal intensity on T2WI may be a sign of malignant transformation.Furthermore,a noted loss of hyperintensity on T1WI and the detection of arterial enhancement might indicate further progression of the histological grade.展开更多
We describe a rare case of the transformation of a dysplastic nodule into well-differentiated hepato- cellular carcinoma (HCC) in a 56-year-old man with alcoholrelated liver cirrhosis. Ultrasound (US) disclosed a 10 m...We describe a rare case of the transformation of a dysplastic nodule into well-differentiated hepato- cellular carcinoma (HCC) in a 56-year-old man with alcoholrelated liver cirrhosis. Ultrasound (US) disclosed a 10 mm hypoechoic nodule and contrast enhanced US revealed a hypovascular nodule, both in segment seven. US-guided biopsy revealed a high-grade dysplastic nodule characterized by enhanced cellularity with a high N/C ratio, increased cytoplasmic eosinophilia, and slight cell atypia. One year later, the US pattern of the nodule changed from hypoechoic to hyperechoic without any change in size or hypovascularity. US-guided biopsy revealed well-differentiated HCC of the same features as shown in the first biopsy, but with additional pseudoglandular formation and moderate cell atypia. Moreover, immunohistochemical staining of cyclase- associated protein 2, a new molecular marker of well- differentiated HCC, turned positive. This is the first case of multistep hepatocarcinogenesis from a dysplastic nodule to well-differentiated HCC within one year in alcohol-related liver cirrhosis.展开更多
Contrast-enhanced ultrasound(CEUS)using microbubble contrast agents are useful for the diagnosis of the nodules in liver cirrhosis.CEUS can be used as a problem-solving method for indeterminate nodules on computed tom...Contrast-enhanced ultrasound(CEUS)using microbubble contrast agents are useful for the diagnosis of the nodules in liver cirrhosis.CEUS can be used as a problem-solving method for indeterminate nodules on computed tomography(CT)or magnetic resonance imaging(MRI)or as an initial diagnostic test for small newly detected liver nodules.CEUS has unique advantages over CT and MRI including no renal excretion of contrast,real-time imaging capability,and purely intravascular contrast.Hepatocellular carcinoma(HCC)is characterized by arterial-phase hypervascularity and later washout(negative enhancement).Benign nodules such as regenerative nodules or dysplastic nodules are usually isoechoic or slightly hypoechoic in the arterial phase and isoechoic in the late phase.However,there are occasional HCC lesions with atypical enhancement including hypovascular HCC and hypervascular HCC without washout.Cholangiocarcinomas are infrequently detected during HCC surveillance and mostly show rimlike or diffuse hypervascularity followed by rapid washout.Hemangiomas are often found at HCC surveillance and are easily diagnosed by CEUS.CEUS can be effectively used in the diagnostic work-up of small nodules detected at HCC surveillance.CEUS is also useful to differentiate malignant and benign venous thrombosis and to guide and monitor the local ablation therapy for HCC.展开更多
目的评价3.0 T MRI检查在肝硬化再生性结节(RN)、异型增生性结节(DN)和小肝癌(SHCC)诊断和鉴别诊断中价值。方法回顾性分析经病理检查确诊的69例RN、DN及SHCC患者的3.0 T MRI平扫及容积采集技术(LAVA)三期动态增强扫描特点。结果 RN主...目的评价3.0 T MRI检查在肝硬化再生性结节(RN)、异型增生性结节(DN)和小肝癌(SHCC)诊断和鉴别诊断中价值。方法回顾性分析经病理检查确诊的69例RN、DN及SHCC患者的3.0 T MRI平扫及容积采集技术(LAVA)三期动态增强扫描特点。结果 RN主要表现为T2WI低信号,动态增强方式呈"缓慢上升型";DN主要表现为T2WI高、低信号,信号较均匀结节的动态方式以"速升缓降型"为主,可有"结中结"(特征表现);SHCC主要表现为T1WI低信号、T2WI高信号,动态增强方式为"速升速降型"。结论肝硬化结节及小肝癌在3.0 T MRI上各有较为典型的表现,临床可据此进行诊断与鉴别诊断;对其他强化类型的肝脏病灶应结合肿瘤血管的扭曲增粗及包膜等表现排除SHCC。展开更多
目的探讨免疫组化标志物热休克蛋白70(heat shock protein 70,HSP70)、磷脂酰肌醇蛋白聚糖3(glypican 3,GPC3)、谷氨酰胺酶(glutamine synthetase,GS)和正醛酮还原酶家族中单分子醛糖还原酶(aldo-ketoreductase family 1 member B10,AKR...目的探讨免疫组化标志物热休克蛋白70(heat shock protein 70,HSP70)、磷脂酰肌醇蛋白聚糖3(glypican 3,GPC3)、谷氨酰胺酶(glutamine synthetase,GS)和正醛酮还原酶家族中单分子醛糖还原酶(aldo-ketoreductase family 1 member B10,AKR1B10)在肝脏高度异型增生结节(high-grade dysplastic nodule,HGDN)和高分化小肝细胞癌(well-differentiated small hepatocellular carcinoma,WD-SHCC)中的表达特点及鉴别诊断价值。方法对16例单结节型HGDN和32例WD-SHCC进行HSP70、GPC3、GS和AKR1B10免疫组化染色。结果 4项标志物在HGDN与WD-SHCC组织中均可表达,单项标志物中,HSP70在HGDN与WD-SHCC中阳性率最高(31.25%,81.25%,P<0.001);GPC3在HGDN与WD-SHCC中阳性率最低(12.50%,25.00%,P<0.460)。HSP70+GPC3+GS及HSP70+AKR1B10+GS诊断组合均在3项标志物中至少2项阳性时,获取最佳诊断效果,此时诊断敏感性和准确率分别为62.50%、81.25%和70.83%、83.33%,特异性均为87.50%。结论HSP70、GPC3和GS经典免疫组化诊断谱对HGDN和WD-SHCC组织具有一定的鉴别能力。然而,GPC3在WD-SHCC中阳性率较低,表达水平与HGDN无明显差异,制约该谱的整体诊断效果。AKR1B10替代GPC3后,在维持较高特异性一致的同时,可明显提高诊断敏感性和准确率。展开更多
基金Supported by the fund from the Korea Science and Engineering Foundation (Grant No. R01-2001-00098). Seung Oe Lim was supported by BK21 Research Fellowship from the Ministry of Education and Human Resources Development
文摘AIM: Expression of heat shock proteins (HSPs) is frequently up-regulated in hepatocellular carcinoma (HCC), which evolves from dysplastic nodule (DN) and early HCC to advanced HCC. However, little is known about the differential expression of HSPs in multistep hepatocarcinogenesis. It was the purpose of this study to monitor the expression of HSPs in multistep hepatocarcinogenesis and to evaluate their prognostic significance in hepatitis B virus (HBV)related HCC.METHODS: Thirty-eight HCC and 19 DN samples were obtained from 52 hepatitis B surface antigen-positive Korean patients. Immunohistochemical and dot immunoblot analyses of HSP27, HSP60, HSP70, HSP90, glucoseregulated protein (GRP)78, and GRP94 were performed and their expression at different stages of HCC development was statistically analyzed.RESULTS: Expression of HSP27, HSP70, HSP90, GRP78, and GRP94 increased along with the stepwise progression of hepatocarcinogenesis. Strong correlation was found only in GRP78 (Spearman's r= 0.802). There was a positive correlation between the expressions of GRP78, GRP94, HSP90, or HSP70 and prognostic factors of HCC. Specifically, the expression of GRP78, GRP94, or HSP90 was associated significantly with vascular invasion and intrahepatic metastasis.CONCLUSION: The expressions of HSPs are commonly up-regulated in HBV-related HCCs and GRP78 might play an important role in the stepwise progression of HBVrelated hepatocarcinogenesis. GRP78, GRP94, and HSP90 may be important prognostic markers of HBV-related HCC, strongly suggesting vascular invasion and intrahepatic metastasis.
文摘AIM: To design a classification tool for the histological assessment of hepatocellular carcinoma (HCC), dysplastic nodules (DN), and macroregenerative nodules (MRN) in cirrhotic liver.METHODS: Two hundred and twelve hepatocellular nodules (106 HCC;74 MRN;32 DN) were assessed systematically, quantitatively, and semiquantitatively as appropriate for 10 histological features that have been described as helpful in distinguishing small HCC, DN, and MRN in cirrhotic livers. The data were analyzed by multiple correspondence analysis (MCA).RESULTS: MCA distributed HCC, DN, and MRN as defined by traditional histological evaluation as well as the individual histological variables, in a 'malignancy scale'.Based on the MCA data representation, we created a classification tool, which categorizes an individual nodular lesion as MRN, DN, or HCC based on the balance of all histological features (i.e., vascular invasion, capsular invasion, tumor necrosis, tumor heterogeneity, reticulin loss,capillarization of sinusoids, trabecular thickness, nuclear atypia, and mitotic activity). The classification tool dassified most (83%) of a validation set of 47 nodules in the same way as the routine histological assessment. No discrepandes were present for DN and MRN between the routine histological assignment and the classification tool. Of 25 HCC assigned by routine assessment in the validation set, 8were assigned to the DN category by the classification tool.CONCLUSION: We have designed a classification tool for the histological assessment of HCC and its putative precursors in cirrhotic liver. Application of this tool systematically records histological features of diagnostic importance in the evaluation of small HCC.
文摘AIM:To elucidate the variety of ways early-stage hepatocellular carcinoma(HCC)can appear on magnetic resonance(MR)imaging by analyzing T1-weighted,T2-weighted,and gadolinium-enhanced dynamic studies.METHODS:Seventy-three patients with well-differentiated HCC(wHCC)or dysplastic nodules were retrospectively identified from medical records,and new histological sections were prepared and reviewed.The tumor nodules were categorized into three groups:dysplastic nodule(DN),wHCC compatible with Edmondson-Steiner grade I HCC(w1-HCC),and wHCC compatible with Edmondson-Steiner gradeⅡHCC(w2-HCC).The signal intensity on pre-contrast MR imaging and the enhancing pattern for each tumor were recorded and compared between the three tumor groups.RESULTS:Among the 73 patients,14 were diagnosed as having DN,40 were diagnosed as having w1-HCC,and 19 were diagnosed as having w2-HCC.Hyperintensity measurements on T2-weighted axial images(T2WI)were statistically significant between DNs and wHCC(P=0.006)and between DN and w1-HCC(P=0.02).The other imaging features revealed no significant differences between DN and wHCC or between DN and w1-HCC.Hyperintensity on both T1W out-phase imaging(P=0.007)and arterial enhancement on dynamic study(P=0.005)showed statistically significant differences between w1-HCC and w2-HCC.The other imaging features revealed no significant differences between w1-HCC and w2-HCC.CONCLUSION:In the follow-up for a cirrhotic nodule,increased signal intensity on T2WI may be a sign of malignant transformation.Furthermore,a noted loss of hyperintensity on T1WI and the detection of arterial enhancement might indicate further progression of the histological grade.
文摘We describe a rare case of the transformation of a dysplastic nodule into well-differentiated hepato- cellular carcinoma (HCC) in a 56-year-old man with alcoholrelated liver cirrhosis. Ultrasound (US) disclosed a 10 mm hypoechoic nodule and contrast enhanced US revealed a hypovascular nodule, both in segment seven. US-guided biopsy revealed a high-grade dysplastic nodule characterized by enhanced cellularity with a high N/C ratio, increased cytoplasmic eosinophilia, and slight cell atypia. One year later, the US pattern of the nodule changed from hypoechoic to hyperechoic without any change in size or hypovascularity. US-guided biopsy revealed well-differentiated HCC of the same features as shown in the first biopsy, but with additional pseudoglandular formation and moderate cell atypia. Moreover, immunohistochemical staining of cyclase- associated protein 2, a new molecular marker of well- differentiated HCC, turned positive. This is the first case of multistep hepatocarcinogenesis from a dysplastic nodule to well-differentiated HCC within one year in alcohol-related liver cirrhosis.
文摘Contrast-enhanced ultrasound(CEUS)using microbubble contrast agents are useful for the diagnosis of the nodules in liver cirrhosis.CEUS can be used as a problem-solving method for indeterminate nodules on computed tomography(CT)or magnetic resonance imaging(MRI)or as an initial diagnostic test for small newly detected liver nodules.CEUS has unique advantages over CT and MRI including no renal excretion of contrast,real-time imaging capability,and purely intravascular contrast.Hepatocellular carcinoma(HCC)is characterized by arterial-phase hypervascularity and later washout(negative enhancement).Benign nodules such as regenerative nodules or dysplastic nodules are usually isoechoic or slightly hypoechoic in the arterial phase and isoechoic in the late phase.However,there are occasional HCC lesions with atypical enhancement including hypovascular HCC and hypervascular HCC without washout.Cholangiocarcinomas are infrequently detected during HCC surveillance and mostly show rimlike or diffuse hypervascularity followed by rapid washout.Hemangiomas are often found at HCC surveillance and are easily diagnosed by CEUS.CEUS can be effectively used in the diagnostic work-up of small nodules detected at HCC surveillance.CEUS is also useful to differentiate malignant and benign venous thrombosis and to guide and monitor the local ablation therapy for HCC.
文摘目的评价3.0 T MRI检查在肝硬化再生性结节(RN)、异型增生性结节(DN)和小肝癌(SHCC)诊断和鉴别诊断中价值。方法回顾性分析经病理检查确诊的69例RN、DN及SHCC患者的3.0 T MRI平扫及容积采集技术(LAVA)三期动态增强扫描特点。结果 RN主要表现为T2WI低信号,动态增强方式呈"缓慢上升型";DN主要表现为T2WI高、低信号,信号较均匀结节的动态方式以"速升缓降型"为主,可有"结中结"(特征表现);SHCC主要表现为T1WI低信号、T2WI高信号,动态增强方式为"速升速降型"。结论肝硬化结节及小肝癌在3.0 T MRI上各有较为典型的表现,临床可据此进行诊断与鉴别诊断;对其他强化类型的肝脏病灶应结合肿瘤血管的扭曲增粗及包膜等表现排除SHCC。
文摘目的探讨免疫组化标志物热休克蛋白70(heat shock protein 70,HSP70)、磷脂酰肌醇蛋白聚糖3(glypican 3,GPC3)、谷氨酰胺酶(glutamine synthetase,GS)和正醛酮还原酶家族中单分子醛糖还原酶(aldo-ketoreductase family 1 member B10,AKR1B10)在肝脏高度异型增生结节(high-grade dysplastic nodule,HGDN)和高分化小肝细胞癌(well-differentiated small hepatocellular carcinoma,WD-SHCC)中的表达特点及鉴别诊断价值。方法对16例单结节型HGDN和32例WD-SHCC进行HSP70、GPC3、GS和AKR1B10免疫组化染色。结果 4项标志物在HGDN与WD-SHCC组织中均可表达,单项标志物中,HSP70在HGDN与WD-SHCC中阳性率最高(31.25%,81.25%,P<0.001);GPC3在HGDN与WD-SHCC中阳性率最低(12.50%,25.00%,P<0.460)。HSP70+GPC3+GS及HSP70+AKR1B10+GS诊断组合均在3项标志物中至少2项阳性时,获取最佳诊断效果,此时诊断敏感性和准确率分别为62.50%、81.25%和70.83%、83.33%,特异性均为87.50%。结论HSP70、GPC3和GS经典免疫组化诊断谱对HGDN和WD-SHCC组织具有一定的鉴别能力。然而,GPC3在WD-SHCC中阳性率较低,表达水平与HGDN无明显差异,制约该谱的整体诊断效果。AKR1B10替代GPC3后,在维持较高特异性一致的同时,可明显提高诊断敏感性和准确率。
