Evaluation of leucocyte adherence inhibition in hepatocellular carcinoma.

The value of the leucocyte adherence inhibition (LAI) test in the diagnosis of hepatocellular carcinoma (HCG) was investigated in 36 patients with this tumour. The sensitivity and specificity of the tube LAI test was assessed in 21 patients with HCC, 15 apparently healthy individuals, 9 patients with various forms of benign liver disease and 5 patients with non-hepatic neoplasms. In only 42% of the HCC patients tested was leucocyte adherence to glass reduced to a greater extent than in the healthy controls and in the patients with non-hepatic neoplasms, and the differences were not statistically significant. Moreover, positive results were obtained in 6/9 patients with benign hepatic disease. A further 15 patients were tested against extracts of HCC tissue using the haemacytometer LAI method. Of these, 53% gave positive results. In all, only 17/36 patients (47%) gave positive LAI responses. The test is thus of limited value in the diagnosis of HCC. The high false-negative result rate may be due either to abrogation of the immune response in HCC patients with large tumour burdens or to antigenic heterogeneity in HCC.     

蛋白酶ICH1在原发性肝癌组织中的表达

目的　研究蛋白酶ICH1与原发性肝癌发生的关系。　方法　应用免疫组织化学方法对40例原发性肝癌中蛋白酶ICH1包括ICH1L和ICH1S的表达进行观察。　结果　40例肝癌中15例ICH1L阳性,阳性率为375%,21例ICH1S阳性,阳性率为525%。ICH1表达与肝癌细胞分化无关。正常肝、癌旁肝及癌细胞中ICH1L与ICH1S间的比率(阳性率和阳性细胞百分率)关系发生了变化,ICH1L的比例降低,而ICH1S的比例升高。癌旁肝细胞中ICH1L和ICH1S表达明显高于癌细胞(P<005)。　结论　ICH1表达异常可能与肝细胞癌变有关,蛋白酶ICH1在肝癌发生过程中可能起一定作用。癌旁肝细胞中ICH1异常表达的意义尚不清楚     

Embryonal serum alpha-globulin in cancer patients: diagnostic value

Sera of 308 patients, of whom 242 were suffering from various types of tumours and 66 from non-cancerous diseases, were tested for the presence of αf-globulin. The reaction was positive in 17 out of 28 patients with primary cancer of the liver. Among these there were 18 cases with tumours of the hepatocellular type, and 14 of these gave a positive αf-globulin reaction. The test was negative in 67 patients with metastatic liver tumours. This confirms Tatarinov's (1964) findings indicating that αf-globulin is detected in sera of patients with primary hepatocellular carcinoma. In addition, αf-globulin was found in some patients with mixed hepatocellular and cholangiocellular carcinoma. The fact that the αf-globulin test is usually positive in hepatocellular and mixed liver carcinomas and negative in metastatic liver tumours makes it potentially useful for the differential diagnosis of liver tumours. αf-globulin was found also in the blood of patients with testicular teratoblastoma, which exhibited some elements of embryonal carcinoma. This novel finding cannot be interpreted as yet. The test was negative in other types of testicular tumours.     

Difference in tissue expression of tumour markers CA 19-9 and CA 50 in hepatocellular carcinoma and cholangiocarcinoma.

The expression of tumour markers CA 19-9 and CA 50, defined by the monoclonal antibodies 1116 NS 19-9 (19-9 antibody) and C 50, was studied by the immunoperoxidase technique in formalin-fixed, paraffin-embedded tissue sections from 11 hepatocellular carcinomas and 10 cholangiocarcinomas of the liver, and from specimens of normal liver and liver cirrhosis. The 19-9 and C 50 antibodies react with sialosylfucosyllactotetraose, corresponding to sialylated blood group antigen Lewis, and the C 50 antibody also with another sugar moiety, sialosyllactotetraose. Neither marker was cancer specific. The CA 19-9 and CA 50 antigens are normal constituents of bile ducts. Nine out of 10 cholangiocarcinomas stained for CA 50, and eight out of 10 for CA 19-9. There was no apparent difference between the staining pattern of CA 19-9 and CA 50. Hepatocellular carcinomas were consistently negative for both markers. Thus, hepatocellular carcinomas and cholangiocarcinomas showed a clear difference in the reactivity for tumour marker antigens CA 19-9 and CA 50. This difference might be of clinical importance in the differential diagnosis between hepatocellular carcinoma and cholangiocarcinoma.     

THE EXPRESSION OF CYTOKERATINS IN HUMAN HEPATOCELLULAR AND CHOLANGIOCELLULAR CARCINOMAS

ＴＨＥＥＸＰＲＥＳＳＩＯＮＯＦＣＹＴＯＫＥＲＡＴＩＮＳＩＮＨＵＭＡＮＨＥＰＡＴＯＣＥＬＬＵＬＡＲＡＮＤＣＨＯＬＡＮＧＩＯＣＥＬＬＵＬＡＲＣＡＲＣＩＮＯＭＡＳ￥ＳｕＱｉｎ；苏勤；Ｌｉｕｙａｎｆａｎｇ；刘彦仿（ＤｅｐａｒｔｍｅｎｔｏｆＰａｔｈｏｌｏｇｙ，...     

Immunohistological evaluation of single small hepatocellular carcinoma with negative staining of monoclonal antibody Hepatocyte Paraffin 1

BACKGROUND AND OBJECTIVES: The sensitivity and specificity of the monoclonal antibody Hepatocyte Paraffin 1 (Hep Par 1) for hepatocellular carcinoma (HCC) are very high, and the usefulness for differential diagnosis of hepatic tumors has been reported. However, there are some cases of HCC with negative staining for Hep Par 1. We examined the histopathological features of HCC with negative staining for Hep Par 1. METHODS: We examined 69 samples of single nodular HCC less than 2 cm in greatest dimension, resected from 1985 to 1994 in our hospital, with immunohistological staining for Hep Par 1, cytokeratin 19 (CK 19), MUC-1 glycoprotein (MUC-1), and epithelial membrane antigen (EMA). RESULTS: Hep Par 1 staining was positive in 64 cases (93%) and negative in 5 cases (7%). With regard to the histological structure, 3 of the 5 negative cases were scirrhous HCC. With regard to the grade of histological differentiation, 2 cases were poorly differentiated HCC, 3 cases were moderately differentiated HCC, and no well-differentiated HCC was found in the negative cases. CK 19, MUC-1, and EMA staining were negative in all cases. CONCLUSIONS: It is necessary to recognize the existence of Hep Par 1 negative HCC, in particular scirrhous HCC. This may be due to a different mechanism in the earlier stage of hepatocarcinogenesis.     

丙型肝炎病毒核心抗原及HBxAg在肝硬化、肝细胞肝癌中分布的免疫组化研究

研究丙型肝炎病毒核心抗原在肝硬变、肝细胞肝癌中的分布规律及意义。方法以免疫组织化学方法检测丙型肝炎病毒（ｈｅｐａｔｉｔｉｓＣｖｉｒｕｓ，ＨＣＶ）核心抗原及ＨＢｘＡｇ在肝硬化、肝细胞癌及其癌旁肝组织中的定位及分布。结果ＨＣＶ核心抗原既定位于肝细胞或癌细胞胞核中，又可定位于这些细胞的胞浆中。在不同的病例，有时以胞浆阳性为主，有时以胞核阳性为主，或二者同时存在。肝硬化组织中，ＨＣＶ核心抗原胞浆阳性细胞多呈灶性分布，而核阳性病例阳性细胞则为弥漫分布；肝细胞肝癌中ＨＣＶ核心抗原以弥漫胞核阳性多见，癌旁肝组织多为ＨＣＶ核心抗原胞浆阳性。ＨＣＶ核心抗原在肝硬化、肝细胞肝癌及癌旁肝中的阳性率分别为６７．３％（６６／９８），７５．０％（７８／１０４）及４８．１％（２５／５２），χ２检验，肝细胞癌中核心抗原的胞核阳性率明显高于其在肝硬化及癌旁肝中的胞核阳性率（Ｐ＜０．０１）。核心抗原在肝细胞肝癌中，其细胞核阳性率，明显高于细胞浆阳性率（Ｐ＜０．０１）。结论ＨＣＶ感染在我国肝硬化、肝细胞肝癌中比较普遍，除ＨＢＶ以外，ＨＣＶ可能在我国肝硬化、肝细胞癌的发生中起着重要作用     

检测γ-谷氨酰转移酶mRNA亚型在肝癌早期诊断中的临床价值

背景及目的：与正常肝脏相比,肝癌细胞表达的γ－谷氨酰转移酶（GGT）有一独特的碳水化合物结构,这种GGT可作为肝癌诊断的重要指标。但是,在癌变过程中GGT基因的改变机制尚不清楚,本研究探讨GGTmRNA亚型的转化与原发性肝癌（HCC）发生的关系,寻找肝癌早期诊断的新方法。方法：以RT－PCR方法检测正常对照组,非癌肝病组,肝癌组及肝转移癌肝组织及外周血的三种GTTmRNA亚型（F,H,P亚型）。结果：正常肝组织,非癌肝组织及肝转移癌癌周组织主要的GGTmRNA类型为F亚型,肝癌组织,癌旁组织,及远离组织GGTmRNA-H亚型的阳性率显著高于正常肝脏及非癌肝病肝组织（P＜0．05）,肝癌组织GGTmRNA-F亚型阳性率明显低于正常对照及非癌肝病组（P＜0．05）。在26例HCC眙有12例外周血中检出GGTmRNA-H亚型,AFP阴性的10例HCC中有5例检出GGTmRNA－H亚型。结论：GGTmRNA亚型转化与肝癌发生有密切关系,分析GGT基因可望成为监测肝细胞癌变的灵敏方法。     

丙型肝肝炎病毒核心抗原及HBxAg在肝硬化,肝细胞肝癌中分布的免…

目的研究丙型肝炎病毒核心抗原在肝硬变、肝细胞肝癌中的分布规律及意义。方法以免疫组织化学方法检测丙型为病毒核心抗原及ＨＢｘＡｇ在肝硬化,肝细胞癌及其癌旁肝中的定位有分布。结果ＨＣＶ核心抗的既定位于肝细胞或癌细胞胞核中,又可一于这些细胞的胞浆中。在不同的病例,有时以胞浆阳性为主,有时以胞核了性为主,或二者同时直化组织中,ＨＣＶ核心原胞浆阳性细胞多呈生分布,而核阳性病例性细胞则为弥漫分布;肝细胞肝癌中Ｈ     

人和大鼠肝细胞癌中骨桥蛋白表达的定量检测

目的骨桥蛋白(Osteopontin,OPN)是一种分泌性的磷酸糖蛋白,参与了包括肝癌在内的多种恶性肿瘤的增殖和转移,本文检测了 OPN基因在人肝细胞癌组织和大鼠肝癌模型中的表达。方法实时荧光定量逆转录PCR检测OPN基因表达,二乙基亚硝胺(diethylnitrosamine,DENA)诱导SD大鼠肝癌模型并动态检测在大鼠肝癌发生发展过程中的OPN基因表达。结果在103例人肝细胞癌病例中69例(67％)肝癌组织中OPN基因表达水平高于癌旁组织,其中58例(56％)超过2倍以上,肝癌和癌旁组织中OPN平均表达水平具有明显差异(0．53±0．91和0．11±0．28,P<0．001)。大鼠肝癌模型中随着肝癌的发生和发展OPN表达水平逐渐上升。结论OPN在肝癌组织中高表达并且随着肝癌的发生发展逐渐升高。     

Preliminary application of carbohydrate antigen CA-50 radioimmunoinhibition test in diagnosing and monitoring cancers

Serum CA-50 antigen in the normal individuals and cancer patients was assayed by radioimmunoassay. CA-50, one type of carbohydrate antigens, consisting mainly of sialylated glycolipid (a ganglioside) and sialylated glycoprotein, can be isolated from the primary or metastatic tumors. Using the latest CA-50 antigen radioimmunoinhibition test kits prepared by Steana Diagnostics AB Company, Sweden, the serum CA-50 content was measured in 62 normal individuals, 9 primary hepatocellular carcinomas, 9 liver benign tumors, 23 ovarian or uterine carcinomas, 22 other malignancies and 21 benign tumors. The normal value was 6.05 +/- 4.93 U/ml. The test values in cancer patients were significantly higher than those in normals or benign tumor patients. Taking the normal mean value plus two times of standard deviation as positive, the positive rate was 77.7% for liver cancer, 65.2% for ovary and uterus carcinomas, 50% for the other cancers. There was only one positive in 62 normals with a false positive rate of 1.6%. Furthermore, 19 patients, being in the remission period or cured by effective treatment, gave normal CA-50 value. It is shown that this method can be used in cancer diagnosis, differential diagnosis and the monitor, prediction of prognosis.     

肝细胞癌p53蛋白、增殖细胞核抗原与临床关系的研究

目的　探讨在肝细胞癌中突变型 p5 3蛋白与增殖细胞核抗原 (PCNA)的相互关系及其意义。 方法　应用免疫组化ABC法检测肝细胞癌和肝硬化中 p5 3蛋白及增殖细胞核抗原。 结果　 37例肝细胞癌 (HCC)中 p5 3阳性 19例 ,33例肝硬化标本中p5 3阳性 2例 ,两者有显著差异 (P <0 .0 1) ;HCC中PCNA阳性细胞均数显著高于肝硬化组 (P <0 .0 1) ;p5 3阳性者PCNA阳性细胞数高于p5 3阴性者 (P <0 .0 5 )。p5 3与PCNA两者表达存在显著正相关关系 (r=0 .5 936 2 ,P <0 .0 5 ) ,p5 3表达与年龄、性别、组织分化无关 ,PCNA表达分别与组织分化及血AFP成负相关及正相关。结论　p5 3基因突变在由肝硬化转变为癌过程中是频发事件 ,其表达异常与HCC发生密切相关。PCNA与 p5 3的正相关提示p5 3突变型主要存在于异常增生细胞中 ,且PCNA可反映癌细胞分化及增殖程度 ,可为肝硬变与肝癌关系的探讨及临床诊断、治疗、预后提供参考资料。     

Immunohistochemical investigatigation of migration inhibitory factor-related protein (MRP)-14 expression in hepatocellular carcinoma

Migration inhibitory factor-related protein (MRP)-8 and-14 belong to the S-100 protein family and are associated with myeloid cell differentiation. MRP is also expressed in some epithelia. However, there are few reports for the investigation on carcinomas. Using the monoclonal antibody 60B8 against MRP-14, we carried out the immunohistochemical evaluation of MRP-14 expression in 70 cases of hepatocellular carcinoma (HCC), and examined the relation to tumor differentiation and vascular invasion. Positively stained tumor cells were detected in 32 cases, all of which belonged to grade II (7/30) or grade III (25/25) of the Edmondson-Steiner classification. In particular, the grade III HCC showed a significantly greater positive reaction. Immunopositivity in the non-carcinomatous hepatocytes and bile duct epithelia was not observed. These findings suggested that malignant hepatocytes newly express MRP-14 and that the neo-expression in differentiated HCC is related to the tumor differentiation and shows higher correlation in the poorly differentiated carcinomas. Furthermore, the cholangiocellular carcinoma and metastatic adenocarcinoma as control materials also presented a more marked immunoreactivity for MRP-14 in the poorly differentiated carcinomas, in a similar manner with the findings of the HCC. Accordingly, MRP is considered to be frequently neo-expressed in poorly differentiated carcinomas. MRP-14 expression rate in the 48 HCC cases with vascular invasion was 56%, showing no significant difference compared with non-invasive tumors.     

肝细胞癌多基因甲基化异常及其临床意义

目的 探讨肝细胞癌中多基因甲基化异常的发生率,研究肝细胞癌中多基因甲基化异常的临床意义.方法 收集60例肝细胞癌及相应的癌旁组织、16例肝炎后肝硬化组织、5例慢性肝炎和5例正常肝组织,筛选消化道肿瘤中APC、RASSF1A、p16、GSTP1、MGMT、DAPK、SOCS-1和RIZ18个甲基化异常频率高的肿瘤抑制基因,应用甲基化特异件聚合酶链反应(MSP)检测8个肿瘤抑制基因在所有标本中的甲基化状态.比较不同基因甲基化与非甲基化肝细胞癌患者的临床病理特征和生存情况.结果 肝细胞癌组织中,RASSF1A、APC、GSTP1、p16、RIZ1和MGMT基因的甲基化率分别为95.0%、90.0%、73.3%、65.0%、61.6%和60.0%,均高于相应的癌旁组织(均P＜0.05);癌旁组织中,MGMT、GSTP1和RIZ1基因的甲基化率分别为41.6%、40.0%和25.0%,均高于肝硬化组织(均P＜0.05).p16基因甲基化的肝细胞癌患者的平均年龄大于非甲基化者;巨块性肝细胞癌中,MGMT基因甲基化者的比例高于非甲基化者;MGMT基基甲基化者的无瘤生存期短于非甲基化者.结论 不同基因在肝细胞癌、癌旁和肝硬化组织中的甲皋化率差异显示了肝细胞癌发生中渐进的表观遗传学改变;GSTP1、RIZ1和MGMT基因的甲基化异常具有肿瘤风险评估和早期诊断价值,而MGMT基因的甲基化异常同时具有预后评估价值.     

A case–control study on family history of liver cancer as a risk factor for hepatocellular carcinoma in North Italy

Objectives: We carried out a case–control study to investigate the role of history of liver cancer in a first-degree relative as a risk factor for hepatocellular carcinoma (HCC).Methods: Two hundred eighty-seven HCC incident cases and 450 subjects unaffected by liver disease (controls) were enrolled in the study. Family history of liver cancer and other malignancies and history of alcohol intake were collected by face-to-face interview. Blood samples were analyzed for HBsAg, anti-HCV and HCV RNA positivity.Results: Family history of liver cancer was associated with HCC (odds ratio [OR] = 2.4; 95% confidence interval [CI] = 1.2–4.7), whereas family history of other malignancies was not (OR = 1.0; 95% CI = 0.6–1.5). An increased OR for family history of liver cancer was found among subjects negative for the other risk factors (OR = 2.0; 95% CI = 0.6–6.9). A synergism of family history of liver cancer was also evident with hepatitis B and hepatitis C virus infection and with heavy alcohol intake.Conclusions: This study suggests a role of family history independent from and interacting with known risk factors for hepatocellular carcinoma.     

Primary hepatic malignancies: resection or liver transplantation?

Liver transplantation in malignancies must be confined to patients with potentially curable disease. The indication is widely accepted, however, in non-resectable tumors or in patients with cirrhosis that excludes major resection. Without treatment prognosis is extremely poor in these patients. In our own experience 12 out of 13 non-cirrhotic patients with hepatocellular carcinoma (HCC) died within 9 months, and 17 out of 19 cirrhotic patients died within the first year of non-curative or explorative surgery. None of our patients with HCC in non-cirrhotic livers has lived longer than 38 months, and those with cirrhotic livers more than 61 months even after curative resection. After liver transplantation 1-year survival rate was 54% in 14 patients with primary hepatic carcinomas (12 HCC, 2 CCC). In cirrhotic patients with large or infiltrating HCC the results of resection are worse than after grafting, at least in the Western World, so liver transplantation must be taken into consideration. The lack of grafts limits treatment by transplantation in these patients. Transplantation is only exceptionally indicated for patients with metastatic liver disease.     

人肝细胞癌及癌旁组织中p53蛋白和PCNA的表达

应用免疫组化方法检测了７３例肝细胞癌及癌旁组织中ｐ５３蛋白的表达，７０例肝细胞癌及癌旁组织中ＰＣＮＡ的表达。结果ｐ５３蛋白、ＰＣＮＡ在肝细胞癌中阳性表达率显著高于癌旁组织，且与肝细胞癌分化程度密切相关。癌旁组织中，ｐ５３蛋白表达仅见于增生结节中，肝硬化组织均为阴性；增生结节中ＰＣＮＡ阳性表达显著高于肝硬化组织。提示ｐ５３基因突变是肝细胞癌的频发事件，在肝细胞癌的发生发展中起重要作用；增生结节细胞的增殖活性增强，是肝细胞癌的癌前病变。作者还讨论了ｐ５３蛋白和ＰＣＮＡ表达间的关系     

HCV核心抗原、NS3抗原在肝癌及癌旁肝组织的表达及意义

 采用SP法（链菌素抗生物素蛋白—过氧化酶连结法）检测46例肝细胞癌及其38例癌旁肝组织中HCV核心抗原、NS3抗原和HBsAg。结果在癌组织中的检出率分别为21．7％、23．9％和19．6％，癌旁组织中的检出率分别36．8％、39．5％和78．9％，核心抗原、NS3抗原伴HBsAg者分别为23.9％和19．6％，不伴HBsAg者分别为10．9％和13％；HBsAg不伴HCV核心抗原、NS3抗原者分别为47．8％和50％。两种HCV抗原均定位于肝细胞和肝癌细胞的胞浆内，在癌旁组织中均有围核分布的特点，其阳性染色细胞呈弥漫、灶状和散在分布。本研究结果提示HCV核心抗原、NS3抗原的检测有可能作为HCV感染的新标志物；HCV和HBV与肝细胞癌的发生可能密切相关，部分患者与HBV和HCV的双重感染可能有关；HCV核心抗原、NS3抗原在肝癌发生中的真正作用，尚待研究。     

Molecular diagnosis of primary liver cancer by microsatellite DNA analysis in the serum

Frequent loss of heterozygosity of microsatellites markers on specific chromosomal region have been reported in various types of primary human cancer. The same loss of heterozygosity has also been identified in the matched plasma/serum DNA. Using 109 microsatellite markers representing 24 chromosomal arms, we have examined the loss of heterozygosity in 21 cases of hepatocellular carcinoma, six of cholangiocarcinoma, and 27 cases of chronic hepatitis or cirrhosis. All cases of the hepatocellular carcinoma showed deletion from two to 10 chromosomal arms, while deletion of chromosomes from two to eight regions was detected in five of six cholangiocarcinoma patients. One or more loss of heterozygosity in the paired serum DNA could be detected in 16 of 25 (76.2%) hepatocellular carcinoma patients. In contrast, no alterations in serum DNA test could be found in cholangiocarcinoma patients. Five of seven (71.4%) hepatocellular carcinoma patients with alpha-fetoprotein levels less than 20 ng ml(-1) produced positive serum DNA test. The profiles of 19 microsatellite markers gave a 100% positive predictive value and an 80.8% negative predictive value for hepatocellular carcinoma. In conclusion, we have determined a profile of microsatellite markers appropriate for differential diagnosis of primary liver cancer. The discovery may permit a high-throughput screening of hepatocellular carcinoma at an early stage of disease.     

应用原位PCR法检测肝癌组织中的HBV DNA

目的 探讨乙型肝为病毒（ＨＢＶ）与肝细胞癌（ＨＣＣ）的关系。方法 采用直接原位聚合酶链反应（ｉｎｓｉｔｕＰＣＲ，ＩＳＰＣＲ）对６４例福尔马林固定石蜡包埋的ＨＣＣ组织（其中６１例附癌周组织）切片中的ＨＢＶＤＮＡ进行检测，与并传统的免疫组织化学原位杂交和组织抽提酸ＰＣＲ法进行了比较。结果 ＩＳＰＣＲ对石蜡包埋的ＨＣＣ组织中ＨＢＶＤＮＡ检测高度敏感，检出率为７１．９％（４６／６４），而相应组织应用免疫组