Proliferating cell nuclear antigen assessed by a computer-assisted image analysis system in patients with chronic viral hepatitis and cirrhosis

BACKGROUND: Assessment of liver cell proliferation by immunodetection of proliferating cell nuclear antigen may predict regenerative potential and survival of liver and hepatocellular carcinoma risk in patients with chronic viral hepatitis. AIM: To evaluate proliferating cell nuclear antigen status and its clinical significance in a large cohort of patients with chronic viral hepatitis and different degree of liver damage by a computer assisted imaging analysis system. MATERIALS: Liver biopsies from 358 patients with chronic hepatitis (259 males, 49 years, 63% with hepatitis C infection, 27% with hepatitis B virus, 10% with multiple infections) were studied. METHODS: Proliferating cell nuclear antigen was localised by immunoperoxidase on microwave oven pre-treated formalin-fixed, paraffin embedded sections using PC10 monoclonal antibody. Proliferating cell nuclear antigen labelling index was calculated by an automated imaging system (Immagini e Computers, Milan, Italy). RESULTS: Mean proliferating cell nuclear antigen labelling index ranged from 0.1% for patients with minimal changes to 3.6% for those with cirrhosis and hepatocellular carcinoma. Overall, proliferating cell nuclear antigen labelling index was higher in males, in older patients, in multiple infections and in hepatitis C virus compared to hepatitis B virus related cases. By linear regression analysis, proliferating cell nuclear antigen labelling index correlated with older age, male gender; higher transaminase levels, hepatitis C virus, higher histological gradIng and staging: by multivariate analysis male gender, hepatitis C virus, higher grading and staging resulted as independent variables. Both hepatitis C virus or hepatitis B virus cirrhotics had similar liver cell proliferation rate but those with hepatitis B virus had higher prevalence of liver cell dysplasia with respect to those with hepatitis C virus. CONCLUSIONS: Proliferating cell nuclear antigen labelling index was a reliable assay for assessing liver cell proliferation rate in patients with chronic viral hepatitis and correlated with liver disease severity     

Immunohistochemical detection of proliferating cell nuclear antigen in hepatocellular carcinoma: Relationship to histological grade

Proliferating cell nuclear antigen (PCNA), also known as cyclin, is an auxiliary protein of DNA polymerase-δ and is found only in the nuclei of proliferating cells in the late G₁ and S phases. The proliferation of hepatocellular carcinoma (HCC) by immunohistochemical staining for PCNA using paraffin sections of 20 surgically resected HCC specimens was analysed. The mean percentage of PCNA-positive nuclei in the HCC tissue was 10.3% in grade I of Edmondson and Steiner's classification, 25.5% in grade II, 28.4% in grade III and 41.5% in grade IV. In early HCC, we observed only a few PCNA-positive tumour cells. However, PCNA-positive nuclei were numerous in the tumour thrombi found in portal vein branches, in regions of extracapsular tumour growth, and in the inner nodules of tumours with a nodule-in-nodule formation. Proliferating cell nuclear antigen positivity was correlated with an increase of the nucleocytoplasmic ratio of tumour cells as determined by image analysis. Our findings showed that PCNA positivity was correlated with the histological grade and invasiveness of HCC, suggesting that this antigen may be used as an indicator to predict tumour invasion in patients with HCC.     

Clinicopathological study of proliferating cell nuclear antigen (PCNA) of hepatocytes in primary biliary cirrhosis

The DNA synthesis activities of hepatocytes in primary biliary cirrhosis (PBC) and other chronic liver diseases and control subjects were examined by staining proliferating cell nuclear antigen (PCNA) with anti-PCNA monoclonal antibody. The number of PCNA-positive cells (PCNA value) was significantly higher in PBC (375±281 parts per thousand; ppt) than in other chronic liver diseases, i.e., chronic hepatitis (95±83 ppt), liver cirrhosis (72±71 ppt), and alcoholic liver disease (73±56 ppt), and in control subjects (11±14 ppt). The PCNA value of PBC in stages I-III of Scheuer's classification was remarkably high, while in stage IV it was low. Even in identical, Scheuer's stages, the PCNA value of PBC was higher in patients who were not given ursodeoxycholic acid (UDCA) than in those who received UDCA. In identical patients, the PCNA value was lowered significantly after UDCA treatment. It was concluded that the DNA synthesis activity of PBC in stages I-III was accelerated and that UDCA can alleviate the abnormality in DNA synthesis activity.     

Perihilar cholangiocarcinoma arising in hepatitis C virus-related liver cirrhosis with hepatocellular carcinoma

Liver cirrhosis is reportedly one of the conditions preceding peripheral-type intrahepatic cholangiocarcinoma but not hilar/perihilar cholangiocarcinoma. Herein, we report a case of perihilar cholangiocarcinoma arising in a hepatitis C virus-related cirrhotic liver. The patient was a 69-year-old man. He was diagnosed with hepatitis C virus-related chronic hepatitis at the age of 56 years, and 9 years later, multiple hepatocellular carcinomas were detected by imaging modalities. Despite treatments, including chemotherapy, he died of hepatic failure at the age of 69 years. At autopsy, in addition to multiple nodules of hepatocellular carcinoma, we found a white mucinous and fibrous tumor spreading from the hepatic hilum to the periphery along the left lateral segmental bile ducts in the advanced cirrhotic liver. This tumor was histologically a cholangiocarcinoma that involved mainly the peribiliary glands and showed variable cystic dilation, suggesting that it might have been derived from these peribiliary glands. Immunohistochemically, the cholangiocarcinoma cells were positive for cytokeratin 7 and mucin core protein 1, and negative for cytokeratin 20 and mucin core protein 2. Hilar/perihilar cholangiocarcinoma arising in hepatitis C virus-related liver cirrhosis has rarely been reported. This case warrants further studies to clarify the possible involvement of hepatitis C virus in tumorigenesis of hilar/perihilar cholangiocarcinoma.     

肝细胞癌和肝硬化组织中增殖细胞核抗原及Ki-67抗原的表达及意义

为探讨肝细胞癌 (HCC)和肝硬化组织中增殖细胞核抗原 (PCNA)及 Ki- 67抗原的表达及意义 ,采用免疫组织化学技术检测 PCNA和 Ki- 67抗原在 HCC和肝硬化组织中的标记指数 (L I)。结果显示 , 、 、 级 HCC的 PCNA L I分别为 (2 6.9± 17.4) %、 (3 3 .1± 2 2 .7) %、 (73 .8± 16.3 ) % ,各级之间差异均有显著性(P均 <0 .0 5 ) ;Ki- 67L I分别为 (2 5 .8± 15 .6) %、 (5 8.2± 18.6) %、 (75 .3± 2 0 .2 ) % ,各级之间差异均有显著性 (P均 <0 .0 5 ) ;但各级 HCC中的 PCNA L I和 Ki- 67L I差异均无显著性 (P均 >0 .0 5 )。肝硬化组织中 PCNAL I为 (8.8± 5 .2 ) % ,Ki- 67L I为 (7.9± 4.4) % ,两者之间差异无显著性 (P>0 .0 5 )。提示 HCC及肝硬化组织中 PCNA和 Ki- 67抗原的阳性率基本一致 ,HCC的分化程度与 PCNA或 Ki- 67密切相关 ;原位检测 HCC组织中PCNA或 Ki- 67抗原的表达 ,有助于判断 HCC分化程度及预后     

肝硬化患者肝组织中PCNA和Ki-67的表达

目的:探讨乙型肝炎和丙型肝炎肝硬化患者肝组织中PCNA和Ki-67抗原的表达及意义.方法:选择58例(乙肝肝硬化24例、丙肝肝硬化22例、慢性肝炎12例)肝脏标本,做H-E染色观察肝组织的病理改变;利用天狼红染色切片检测肝组织内胶原纤维的面密度;采用免疫组织化学SP法观察肝组织中PCNA和Ki-67抗原的表达,并检测阳性细胞的标记指数(labelingindex,LI).结果:肝硬化胶原纤维的面密度百分比与慢性肝炎比较(12.2%±3.1%vs1.40%±1.0%,P<0.001)明显增高,乙型与丙型肝炎肝硬化胶原纤维的面密度百分比无明显差异(P>0.05);慢性肝炎与肝硬化比较PCNA和Ki-67LI(34.67%±8.6%vs10.38%±3.76%,2.81%±0.51%vs1.69%±1.03%,均P<0.001)明显增高;丙肝肝硬化与乙肝肝硬化比较PCNA和Ki-67LI(13.12%±1.42%vs6.32%±2.18%,2.48%±0.54%vs0.95%±0.77%,均P<0.001)均明显增高;肝硬化胶原纤维的面密度与PCNA和Ki-6LI之间无相关性(P>0.05).结论:肝硬化组织中肝细胞增殖指数比慢性肝炎低,但丙型肝炎肝硬化的肝细胞增殖指数比乙型肝炎肝硬化高;PCNA和Ki-67LI与肝硬化胶原纤维面密度无相关性.     

大黄素对肾脏系膜细胞增殖细胞核抗原的影响

本文应用体外细胞培养和免疫组化技术,以增殖细胞核抗原(PCNA/cyclin)为标志抗原,观察了大黄素对肾小球系膜细胞周期调控的影响,发现大黄素能明显抑制系膜细胞向S期的转化。我们以往的工作已证实大黄素能抑制肾小球系膜细胞c-myc原癌基因mRNA的表达,并可能通过阻抑系膜细胞由G_1期向S期转化,进而抑制系膜细胞增殖。本项研究通过观察大黄素对细胞周期S期标志抗原(PCNA/cyclin)的影响,进一步证实了上述理论。     

Multivariate analysis of risk factors for hepatocellular carcinoma in patients with hepatitis C virus-related liver cirrhosis

To elucidate the risk factors for hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-related liver cirrhosis (LC), we examined 204 cirrhotic patients negative for hepatitis B surface antigen and positive for HCV antibodies. The independent influence of various clinical characteristics in these patients was analyzed by multiple logistic regression, and the risk factors for HCC were identified. Multiple logistic regression analysis identified and ranked the following four risk factors: male sex (P<0.001), habitual heavy drinking (P<0.005), hepatitis B virus antibody positivity (anti-HBs and/or anti-HBc,P<0.05), and age greater than 60 years (P<0.05). The odds ratio of HCC was 4.20 (95% confidence interval; CI, 1.80–9.78) in male patients, 3.27 (95% CI, 1.46–7.30) in habitual heavy drinkers, 2.01 (95% CI, 1.01–3.99) in patients positive for hepatitis B virus antibodies, and 2.06 (95% CI, 1.00–4.23) in patients older than 60 years. The cumulative occurrence rates of HCC after blood transfusion were significantly higher in habitual heavy drinkers (4.8%, 49.4%, and 74.7% at 10, 20, and 30 years, respectively) than in non-drinkers (0%, 21.0%, and 23.3% at 10, 20, and 30 years, respectively,P<0.0003). The mean interval for progression to LC after blood transfusion was significantly shorter in the habitual heavy drinkers than in the non-drinkers (22.4±4.4 years vs 28.4±3.9 years;P<0.0003). This multivariate analysis revealed that habitual heavy drinking and hepatitis B virus antibody positivity are significant risk factors for HCC in HCV-related liver cirrhosis. This work was presented in preliminary form at the annual meeting of the American Association for Study of Liver Diseases, New Orleans, May 16, 1994 and published as an abstract inGastroenterology 14: A875, 1994.     

大肠癌微血管密度及增殖细胞核抗原与临床预后的关系

目的探讨大肠癌微血管密度(MVD)及增殖细胞核抗原(PCNA)与手术后有无潜在性肿瘤转移及复发的相关性.方法对55例大肠癌进行术后5 a的随访及石蜡标本的S-P免疫组化法染色. 结果大肠癌MVD与其分化程度密切相关(P＜0.01);与临床病理分期(Dukes')间差异有显著意义(P＜0.05);与有无淋巴结、肝转移密切相关(P＜0.05);在术后复发与无复发生存者间差异有非常显著性意义(P＜0.01).增殖活性表达提示,分化愈差,有淋巴结或肝转移时,增殖活性增高,术后复发与无复发生存者之间,增殖活性差异有显著意义(P＜0.05).结论大肠癌MVD及PCNA与肿瘤的浸润、淋巴结及肝转移相关.手术时虽无明显转移,但MVD增高及PCNA活性增强,提示可能有潜在的转移存在.     

Helicobacter infection in patients with HCV-related chronic hepatitis,cirrhosis, and hepatocellular carcinoma

Chronic hepatitis may progress to cirrhosis and hepatocellular carcinoma (HCC). HCC represents one of the most common human cancers. Incidence rates for this tumor vary widely on a worldwide, suggesting that environmental factors such as infectious microorganisms, carcinogens, or nutrition play a role in its pathogenesis. Several Helicobacter spp. colonize the liver of animals and induce hepatitis. The aim of this study was to determine whether Helicobacter infection was associated with HCV-related liver diseases in humans. Liver tissue samples, including biopsy and surgically excised tissues, were collected from patients positive for hepatitis C viruses (HCV) RNA in the serum. Genomic DNA was extracted from sections of formalin-fixed paraffin-embedded tissues by using the QIAamp Tissue Kit and subjected to polymerase chain reaction (PCR) analysis using two sets of Helicobacter-specific 16S ribosomal RNA primers. To identify positive samples for H. pylori, a set of primers specific for a conserved region in the H. pylori vacA gene were also used. The patients' H. pylori status was determined by ELISA. Forty-one patients (mean age 54.9, range 19–78 years; 24 men) were studied. Thirty patients had chronic viral hepatitis (CH) without (N = 18) or with (N = 12) cirrhosis (CIR), and 11 patients had HCC. Anti-H. pylori IgG was detected in 54%. The expected 422- and 210-bp fragments of Helicobacter 16S rRNA were amplified from 27% of liver samples, including 17% of CH-CIR and 55% of HCC (P = 0.004). The vacA sequence was amplified in 10 of 41(24%) samples (27% of those with HCC).: These data confirm the presence of H. pylori DNA sequences in human liver and suggest an association of Helicobacter spp. with HCV-related chronic liver diseases. Further studies are needed to ascertain whether Helicobacter spp. infection plays a role in the development of HCC.     

莪术油对小鼠肝癌增殖细胞核抗原的影响

目的揭示莪术油对小鼠肝癌细胞增殖活性的抑制作用．方法用莪术油进行２次抑制小鼠肝癌ＨｅｐＡ实验．以抗增殖细胞核抗原（ＰＣＮＡ）免疫组化染色方法,评估莪术油对小鼠肝癌细胞增殖活性的影响．结果莪术油对小鼠肝癌ＨｅｐＡ的抑瘤率分别为５２％和５１％,与对照组比有显著性差异（Ｐ＜００１）．经莪术油作用过的小鼠ＨｅｐＡ肝癌细胞的ＰＣＮＡ阳性指数（ＰＣＮＡ－ＰＩ）为３０±４,显著低于对照组４０±６（Ｐ＜００１）．结论莪术油抑制小鼠肝癌生长可能与其抑制ＰＣＮＡ表达有关．     

Correlation between ultrasonographic and pathologic diagnoses of hepatitis B and C virus-related cirrhosis

Background. We aimed to evaluate the validity of ultrasonography (US) in the diagnosis of cirrhosis in patients with chronic hepatitis B virus (HBV) or C virus (HCV) infection. Methods: A total of 210 patients, 67 with chronic HBV and 143 with HCV infection, were evaluated for the cirrhotic status of liver by both needle biopsy and US. According to the pathological findings, a fibrosis score 4 on the histology activity index was the gold standard for the diagnosis of cirrhosis. A US scoring system consisting of liver surface, parenchyma, vascular structure, and splenic size was used to describe the severity of hepatic parenchymal damage. Results: Cirrhosis was found in 27 (40%) of the 67 HBV patients and in 51 (36%) of the 143 HCV patients pathologically. The mean fibrosis scores were 0.95, 1.24, 2.35, 2.95, 3.8 and 3.7 in patients with US scores of 4, 5, 6, 7, 8, and 9 or more, respectively. The US scores were significantly correlated with the hepatic fibrosis scores (P < 0.05). Based on the receiver operating characteristic (ROC) curve, a US score of 7 was the best cutoff point for the prediction of HBV-related cirrhosis, with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 77.8%, 92.5%, 87.5%, 86.0%, and 86.6%, respectively. In HCV-related cirrhosis, a US score of 6 provided results of 82.4%, 70.7%, 60.9%, 87.8%, and 74.8%, respectively. The specificity, positive predictive value, and accuracy were significantly higher in patients with HBV than in those with HCV infection (P = 0.012, P = 0.032, and P = 0.079, respectively). Conclusions: Cirrhosis can be predicted well by US, especially in patients with HBV infection. Received: March 22, 2002 / Accepted: July 26, 2002 Reprint requests to: S.-N. Lu Editorial on page 202     

Effect of millimeter wave radiation on the expression of proliferating cell nuclear antigen,CDK4 and P16 in rat hepatocellular carcinoma

OBJECTIVE: To study the effects of millimeter wave (MMW) radiation on rat hepatocellular carcinoma. METHODS: Forty male Wistar rats were randomly divided into four groups, and the liver region of the rats was directly radiated by MMW (35.8 GHz, 100 mW/cm²) for 20 min twice per week. Rats in groups 1 to 3 were fed with diethlnitrosamine (DEN). Group 1 was a tumor control group with sham radiation. Group 2 was given radiation for 10 weeks starting from week 5 and group 3 was radiated for 5 weeks starting from week 10. Group 4 was a normal control group radiated for 5 weeks and given distilled water. At week 14, all rats were sacrificed. A serological test for γ‐glutamyltransferase (γ‐GT) and immunohistochemical staining of proliferating cell nuclear antigen (PCNA), CDK4 and P16 in liver tissue were performed. RESULTS: The serum level of γ‐GT in group 1 (18.44 ± 4.88 U/L) was higher than that in group 2 (13.75 ± 2.41 U/L, P < 0.05), and the level of γ‐GT in group 3 (16.43 ± 2.12 U/L) was lower than that in group 1, but the difference was not significant. Based on histological examination of the livers, adenocarcinoma only developed in group 1. In the other DEN‐induced tumor groups, only eosinophilic and basophilic nodules were formed in the liver; no carcinoma cells were found. Expression of proliferating cell nuclear antigen (PCNA) and CDK4 staining in liver tissue in groups 2 and 3 were significantly lower than those in group 1, but the expression of P16 in the former was higher than that in the latter. CONCLUSIONS: Millimeter wave radiation partially inhibits cell proliferation and suppresses DEN‐induced hepatocellular carcinoma in rats.     

Analyses of proliferating cell nuclear antigen-positive cells in hepatocellular carcinoma: Comparisons with clinical findings

Abstract Proliferating tumour cells in 92 patients with hepatocellular carcinoma (HCC) were identified by an immunohistochemical method using a monoclonal antibody against proliferating cell nuclear antigen (PCNA). The rate of PCNA-positive cells in HCC tissues was positively correlated with histological grade and the tumour size and T factor of the tumour.
In order to analyse the relationship between prognostic factors and cumulative survival rate after obtaining tumour specimens, 49 patients whose clinical courses could be followed after needle biopsy were selected for evaluation. These patients were treated by medical therapy alone. Analyses of prognostic factors by Cox's proportional hazard model revealed that the patient's prognosis was significantly correlated with PCNA-positive rates as well as the tumour size and mode of therapy. Moreover, the cumulative survival rates were significantly ( P < 0.001) higher in patients with rates of PCNA-positive cells <15% than in those with ≧ 15%, even when tumour sizes were under 50 mm or tumours demonstrated the same degree of histological differentiation.
These findings indicate that the PCNA-positive rate in biopsied tissues provides useful prognostic information in patients with HCC treated only by medical therapy.     

Long-term effect of interferon alpha-2b plus ribavirin therapy on incidence of hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis

We assessed the efficacy of interferon (IFN) alpha-2b plus ribavirin therapy in patients with hepatitis C virus (HCV)-related cirrhosis, and elucidated the risk factors for the development of hepatocellular carcinoma (HCC) to determine whether these therapies might reduce the incidence of HCC. One hundred and thirty-two HCV-cirrhotic patients receiving IFN alpha-2b (3 or 5 MU thrice weekly) and oral ribavirin (1,000-1,200 mg/day) for 24 or 48 weeks were analysed. Cumulative incidence of HCC was estimated by the Kaplan-Meier method. The prognostic relevance of clinical variables and HCC occurrence was evaluated by univariate analysis with the log-rank test and by multivariate Cox's regression analysis. A total of 116 patients completed the treatment and 73 (55%) achieved a sustained virological response (SVR). Stepwise logistic regression analysis showed that nongenotype 1b (P < 0.001) and low viral load (P = 0.018) were independent variables of SVR. During a median follow-up period of 37 (12-63) months, HCC developed in 11 patients with non-SVR and five with SVR (P = 0.0178), whereas there was no difference between those with transient biochemical response and nonresponse (P = 0.5970). The Kaplan-Meier method also showed that old age (>or=60 years) (P = 0.0034) and genotype 1b (P = 0.0104) were associated with HCC occurrence. Using Cox's regression analysis, non-SVR (odds ratio = 3.521, P = 0.036), male (odds ratio = 6.269, P = 0.011) and old age (odds ratio = 3.076, P = 0.049) were independent significant risk factors contributing to HCC development. Our results suggest that achieving SVR by IFN alpha-2b plus ribavirin therapy may decrease the incidence of HCC in patients with HCV-related cirrhosis.     

增殖细胞核抗原检测在非霍奇金淋巴瘤中的临床意义

目的　研究非霍奇金淋巴瘤 (NHL)中增殖细胞核抗原 (PCNA)的表达水平 ,探讨其在NHL中的临床意义。方法　应用免疫组化法检测 5 3例NHL患者和 10例淋巴结反应性增生患者 (对照组 )石蜡切片中PCNA的表达。结果　 10例对照组中PCNA表达以淋巴滤泡中心为主 ,均为低度阳性。 5 3例NHL患者PCNA表达全部为阳性 ,但强度明显不同。低度恶性组PCNA表达均为 (+ )～ (+ + ) ,无 (+ + + )者 ,中、高度恶性组均为 (+ + )～ (+ + + ) ,且 (+ + + )占 42 .2 %(19/4 5例 )。Kaplan Meier生存曲线显示 ,PCNA(+ + )组生存率明显高于PCNA(+ + + )组 (P <0 .0 1)。结论　PCNA的表达强度可以作为判断NHL恶性程度和预后的重要参考指标     

慢性脑缺血大鼠海马中APE、PCNA的表达与神经细胞凋亡

目的研究慢性脑缺血大鼠海马中DNA损伤修复相关蛋白脱嘌呤/脱嘧啶核酸内切酶（APE）、增生细胞核抗原（PCNA）的活性变化及神经元的凋亡情况,并探讨三者之间的相关性。方法成年雄性W istar大鼠随机均分为假手术组、持久性双侧颈总动脉结扎（2-VO）1周组、3周组、8周组,用W estern b lotting检测各组海马组织中APE、PCNA蛋白表达水平,用流式细胞仪检测海马神经元的凋亡程度。结果2-VO 1周组APE、PCNA蛋白的表达量明显低于对照组（P〈0.01）,随着2-VO时间的延长其蛋白表达水平逐渐上升,但仍低于对照组（P〈0.05）;慢性脑缺氧大鼠术后1周时海马神经细胞凋亡百分率最高为22.66%,以后随时间的延长细胞凋亡数逐渐下降（P〈0.01）。结论慢性脑缺血大鼠早期APE、PCNA活性下降,同时其神经元凋亡率较高,后期蛋白表达水平逐渐上升,神经元的凋亡程度也逐渐下降,表明DNA损伤与修复失衡所致的神经细胞凋亡是慢性缺血性脑损伤发病的重要机制之一。     

肝细胞癌组织HSP70、p53和PCNA的表达及其意义

目的探讨热休克蛋白70（HSP70）、p53和增殖细胞核抗原（PCNA）在肝细胞癌（HCC）组织中的表达及其意义。方法采用免疫组化法检测正常人、慢性乙型肝炎、肝硬化和HCC肝或癌组织HSP70、p53和PCNA的表达情况。结果 HCC组织HSP70、p53和PCNA表达阳性率明显高于非癌组织（x1^2=27.16x2^2=67.6,x3^2=40.6,P〈0.01）;HSP70在正常人、慢性乙型肝炎、肝硬化和HCC中的表达逐步增强;HSP70和p53在分化较好的HCC中的阳性率明显低于分化不良者（x1^2=6.8,P1〈0.01x2^2=6.1,P2〈0.05）,而PCNA表达与HCC组织分化程度无关（x2=2.4,P〉0.05）;HSP70表达强度与p53和PCNA表达关系密切（x1^2=41.3,x2^2=41.4,P〈0.01）。结论 HCC是HSP70高表达肿瘤。HSP70表达与p53和PCNA表达密切相关,因而在HCC发生和发展中起重要作用。     

Overexpressed cyclo-oxygenase-2 in the background liver is associated with the clinical course of hepatitis C virus-related cirrhosis patients after curative surgery for hepatocellular carcinoma

BACKGROUND: The probable role of cyclo-oxygenase-2 (COX-2) in the development of hepatocellular carcinoma (HCC) in patients with chronic liver diseases has been accepted to be relevant. The purpose of the present study was to determine whether overexpressed COX-2 in the background liver affects the clinical course of hepatitis C virus (HCV)-related cirrhosis patients after curative surgery for HCC. METHODS: Twenty-nine clinical stage I HCC patients with HCV-related cirrhosis, who underwent curative surgery, were enrolled in the present study (22 men and seven women, age range 53-73 years; follow-up period; range 22-159 months, median 61 months). The COX-2 expression in the cirrhotic liver was examined by immunohistochemistry using the avidin-biotin-peroxidase complex technique on paraffin-embedded formalin-fixed tissue. The COX-2 expression was scored, then correlated with monitored alanine aminotransferase (ALT) levels during the follow-up period after surgery, response to alternative therapy aiming to improve elevated ALT levels, and recurrence/survival after surgery. RESULTS: The COX-2 expression scores were significantly higher in the high-ALT group than in the low-ALT group (Mann-Whitney, P = 0.010), and were significantly higher in non-responders to the alternative therapy than in responders (Mann-Whitney, P = 0.028). The higher COX-2 expression in the cirrhotic liver was the significant independent risk factor for residual liver recurrence (Cox multivariate analysis, P = 0.014), but not for survival. CONCLUSIONS: Overexpressed COX-2 in the background liver may play an important role in prolonged acceleration of necroinflammation, resistance to the alternative therapy, and recurrence/new development of HCC in HCV-related cirrhosis patients.     

PCNA,MMP-9预计肝细胞肝癌预后的研究分析

探讨增殖细胞核抗原(PCNA)基质金属蛋白酶(MMP-9)与肝细胞肝癌预后的关系。应用S-P法,对44例患者分别进行PCNA、MMP-9两种免疫组化染色,并对结果进行统计学处理。1.PCNA染色中,(-)～(+)组预后好于(++)～(+++)组(x~2=5.13,P<0.05)。2.MMP-9染色中,癌组织(-)组预后好于(+)组(x~2=4.51,P<0.05);癌旁组织(+)组预后好于(-)组(x~2=4.47,P<0.05)。在术后生存时间<1年的患者的肿瘤细胞中PCNA高表达,说明肝细胞的增殖程度较高。<1年的患者的癌组织中,MMP-9亦高表达,说明肝细胞侵袭力较高;而癌旁组织中MMP-9却低表达,说明宿主的免疫力较低。因此二者均可作为预计肝细胞肝癌预后的指标。