NDRG2和AKT2与其磷酸化蛋白在肝癌病理组织中的应用及与临床病理的相关性研究

目的:探讨N-myc下调基因2(NDRG2)和丝/苏氨酸蛋白激酶2(AKT2)及其磷酸化蛋白(p-AKT2)在肝癌病理组织中的应用及与临床病理的相关性。方法:选择肝癌患者62例作为对象,所有患者均行手术治疗,术中取病灶组织与癌旁组织(距离病灶>5 cm)。采用荧光定量PCR技术测定标本NDRG2、AKT2 mRNA水平;采用Western Blot法测定标本NDRG2、AKT2及p-AKT2水平。结果:肝癌病灶组织与癌旁组织AKT2 mRNA水平差异无统计学意义(P>0.05);肝癌病灶组织中NDRG2 mRNA水平,低于对照组,差异有统计学意义(P<0.05);肝癌病灶组织中NDRG2蛋白水平,低于癌旁组织,差异有统计学意义(P<0.05);肝癌病灶组织中AKT2、p-AKT2蛋白水平,高于癌旁组织,差异有统计学意义(P<0.05)。结论:NDRG2在肝癌组织中呈低表达,而p-AKT2在肝癌组织中呈高表达,二者呈负相关性,均能参与疾病的发生、发展。

Prealbumin is predictive for postoperative liver insufficiency in patients undergoing liver resection

AIM:To investigate the risk factors for postoperative liver insufficiency in patients with Child-Pugh class A liver function undergoing liver resection.METHODS:A total of 427 consecutive patients undergoing partial hepatectomy from October 2007 to April 2011 at a single center(Department of Hepatic SurgeryⅠ,Eastern Hepatobiliary Surgery Hospital,Shanghai,China) were included in the study.All the patients had preoperative liver function of Child-Pugh class A and were diagnosed as having primary liver cancer by postoperative histopathology.Surgery was performed by the same team and hepatic resection was carried out by a clamp crushing method.A clamp/unclamp time of 15 min/5 min was adopted for hepatic inflow occlusion.Patients' records of demographic variables,intraoperative parameters,pathological findings and laboratory test results were reviewed.Postoperative liver insufficiency and failure were defined as prolonged hyperbilirubinemia unrelated to biliary obstruction or leak,clinically apparent ascites,prolonged coagulopathy requiring frozen fresh plasma,and/or hepatic encephalopathy.The incidence of postoperative liver insufficiency or liver failure was observed and the attributing risk factors were analyzed.A multivariate analysis was conducted to determine the independent predictive factors.RESULTS:Among the 427 patients,there were 362 males and 65 females,with a mean age of 51.1 ± 10.4 years.Most patients(86.4%) had a background of viral hepatitis and 234(54.8%) patients had liver cirrhosis.Indications for partial hepatectomy included hepatocellular carcinoma(391 patients),intrahepatic cholangiocarcinoma(31 patients) and a combination of both(5 patients).Hepatic resections of ≤ 3 and ≥ 4 liver segments were performed in 358(83.8%) and 69(16.2%) patients,respectively.Seventeen(4.0%) patients developed liver insufficiency after hepatectomy,of whom 10 patients manifested as prolonged hyperbilirubinemia unrelated to biliary obstruction or leak,6 patients had clinically apparent ascites and prolonged coagulopathy,1 patient had hepatic encephalopathy and died on day 21 after surgery.On univariate analysis,age ≥ 60 years and prealbumin < 170 mg/dL were found to be significantly correlated with postoperative liver insufficiency(P = 0.045 and P = 0.009,respectively).There was no statistical difference in postoperative liver insufficiency between patients with or without hepatitis,liver cirrhosis and esophagogastric varices.Intraoperative parameters(type of resection,inflow blood occlusion time,blood loss and blood transfusion) and laboratory test results were not associated with postoperative liver insufficiency either.Age ≥ 60 years and prealbumin < 170 mg/dL were selected on multivariate analysis,and only prealbumin < 170 mg/dL remained predictive(hazard ratio,3.192;95%CI:1.185-8.601,P = 0.022).CONCLUSION:Prealbumin serum level is a predictive factor for postoperative liver insufficiency in patients with liver function of Child-Pugh class A undergoing hepatectomy.Since prealbumin is a good marker of nutritional status,the improved nutritional status may decrease the incidence of liver insufficiency.

Immunohistochemical analysis of p53,cyclinD1,RB1,c-fos and N-ras gene expression in hepatocellular carcinoma in Iran

AIM： TO study the effect of some genes especially those involved in cell cycle regulation on hepatocellular carcinoma. METHODS： Paraffin-embedded tissue samples of 25 patients （18 males and 7 females） with hepatocellular carcinoma were collected from 22 pathology centers in Tehran during 2000-2001, and stained using immunohistochemistry method （avidin-biotin-peroxidase） for detection of p53, cyclinD1, RB1, c-los and N-ras proteins. RESULTS： Six （24%）, 5 （20%）, 12 （48%） and 2 samples （8%） were positive for p53, cyclinDl, C-los and N-ras expression, respectively. Twenty-two （88%） samples had alterations in the （31 cell-cycle checkpoint protein expression （RBI or cyclinD1）. P53 positive samples showed a higher （9 times） risk of being positive for RBI protein than p53 negative samples. Loss of expression of RBI in association with p53 over-expression was observed in 4 （66.7%） of 6 samples. Loss of expression of RBI was seen in all cyclinD1 positive, 20 （90.9%） N-ras negative, and ii （50%） C-fos positive samples, respectively. CyclinD1 positive samples showed a higher （2.85 and 4.75 times） risk of being positive for c-los and N-ras expression than cyclinD1 negative samples. CONCLUSION： The expression of p53, RB1 and c-los genes appears to have a key role in the pathogenesis of hepatocellular carcinoma in Iran. Simultaneous overexpression of these genes is significantly associated with their loss of expression during development of hepatocellular carcinoma.

Useful detection of CD147 (EMMPRIN) for pathological diagnosis of early hepatocellular carcinoma in needle biopsy samples

AIM:To make clear whether CD147 (EMMPRIN) expression in pathological tumor samples with a fine-needle aspiration biopsy is useful for pathological diagnosis of early hepatocellular carcinoma (HCC). METHODS:Twenty-two patients (15 men and 7 women; median age 68 years,range 56-81 years) underwent a liver tissue biopsy in order to make a diagnosis of HCC. Paraffin-embedded liver biopsy tissue samples from 22 patients were stained with anti-CD147 antibody,murine monoclonal antibody 12C3 (MAb12C3) for immunohistochemical analysis. An immunohistochemical analysis of CD147 was performed and the degree of staining compared between tumor and non-tumor tissue. In addition,the degree of staining within tumor tissue was compared according to a number of clinicopathological variables. RESULTS:The degree of staining of CD147 was significantly higher in tumor tissues than non-tumor tissues,even in tumors less than 15 mm in diameter.The expression of this protein was significantly elevated in HCC tissue specimens from patients with a low value of serum AST and γ-GTP.

Vascular architecture:is it a helpful histopathological biomarker for hepatocellular carcinoma?

Hepatocellular carcinoma(HCC) remains one of the major public health problems throughout the world.Although originally associated with tumorigenic processes,liver angiogenesis has also been observed in the context of different liver in-flammatory,fibrotic,and ischemic conditions.Here we investigate the fractal dimension as a quantitator of non-Euclidean two-dimensional vascular geometry in a series of paired specimens of primary HCC and surrounding non-tumoral tissue,and discuss why this parameter might provide additional information regarding cancer behavior.The application of fractal geometry to the measurement of liver vascularity and the availability of a computer-aided quantitative method can eliminate errors in visual interpretation,and make it possible to obtain closer-to-reality numerals that are compulsory for any measurement process.

Primary hepatic leiomyosarcoma with liver metastasis of rectal cancer

Primary hepatic leiomyosarcoma is a particularly rare tumor with a poor prognosis. Curative resection is currently the only effective treatment, and the efficacy of chemotherapy is unclear. This represents the first case report of a patient with primary hepatic leiomyosarcoma co-existing with metastatic liver carcinoma. We present a 59-year-old man who was diagnosed preoperatively with rectal cancer with multiple liver metastases. He underwent a curative hepatectomy after a series of chemotherapy regimens with modified FOLFOX6 consisting of 5-fluorouracil, leucovorin and oxaliplatin plus bevacizumab, FOLFIRI consisting of 5-fluorouracil, leucovorin and irinotecan plus bevacizumab, and irinotecan plus cetuximab. One of the liver tumors showed a different response to chemotherapy and was diag-nosed as a leiomyosarcoma following histopathological examination. This case suggests that irinotecan has the potential to inhibit the growth of hepatic leiomyosarcomas. The possibility of comorbid different histological types of tumors should be suspected when considering the treatment of multiple liver tumors.

DEC1 nuclear expression:A marker of differentiation grade in hepatocellular carcinoma

AIM: To investigate the expression patterns of human differentiated embryo chondrocyte 1 (DEC1) in hepatocellular carcinoma (HCC) and corresponding adjacent non-tumor and the normal liver tissues, the association between DEC1 expression and histopathological variables and the role of DEC1 in hepatocarcinogenesis. METHODS: The expression of DEC1 was detected immunohistochemically in 176 paraffin-embedded sections from 63 patients with HCC and 50 subjects with normal liver tissues. RESULTS: DEC1 protein was persistently expressed in the cytoplasm of hepatocytes in normal liver and HCC tissues. Compared with adjacent non-tumor liver tissues, HCC tissues showed high nuclear expression of DEC1 protein. However, high DEC1 nuclear expression was more frequently detected in well-differentiated (83.3%) than in moderately (27.3%) and poorly differentiated HCC (16.7%). Low DEC1 expression was associated with poor histological differentiation and malignancy progression. A correlation was found between the nuclear expression of DEC1 protein and histological differentiation (r = 0.376, P = 0.024). CONCLUSION: DEC1 is expressed in the cytoplasm of hepatocytes and because nuclear DEC1 expression is decreased with decreasing differentiation status of HCC, nuclear DEC1 might be a marker of HCC differentiation.

A comparison of survival and pathologic features of non-alcoholic steatohepatitis and hepatitis C virus patients with hepatocellular carcinoma

AIM： To compare the clinical outcome and pathologic features of non-alcoholic steatohepatitis （NASH） patients with hepatocellular carcinoma （HCC） and hepatitic C virus （HCV） patients with HCC （another group in which HCC is commonly seen） undergoing liver transplantation. METHODS： Patients transplanted for HCV and NASH at our institution from January 2000 to April 2011 were analyzed. All explanted liver histology and pre-trans- plant liver biopsies were examined by two specialist liver histopathologists. Patient demographics, disease free survival, explant liver characteristics and HCC features （tumour number, cumulative tumour size, vascular invasion and differentiation） were compared between HCV and NASH liver transplant recipients. RESULTS： A total of 102 patients with NA^SH and 283 patients with HCV were transplanted. The incidence of HCC in NASH transplant recipients was 16.7% （17/102）. The incidence of HCC in HCV transplant recipients was 22.6% （64/283）. Patients with NASH-HCC were statisti- cally older than HCV-HCC patients （P 〈 0.001）. A signif- icantly higher proportion of HCV-HCC patients had vas- cular invasion （23.4% vs 6.4%, P = 0.002） and poorly differentiated HCC （4.7% vs 0%, P 〈 0.001） compared to the NASH-HCC group. A trend of poorer recurrence free survival at 5 years was seen in HCV-HCC patients compared to NASH-HCC who underwent a Liver trans- plantation （P = 0.11）. CONCLUSION： Patients transplanted for NASH-HCC appear to have less aggressive turnout features com- pared to those with HCV-HCC, which likely in part ac- counts for their improved recurrence free survival.

Alpha-fetoprotein-producing rectum adenocarcinoma:A case report

A case with an Alpha-fetoprotein-producing(AFP-producing) carcinoma originating from the rectum was described.A 41-year-old man,who underwent a palliative surgery for rectal carcinoma,was diagnosed with occupying liver lesions and a remarkable AFP elevation(3484.61 ng/mL),and the AFP declined obviously 10 days after the palliative surgery.So we carried out a biopsy of the liver lesions.The histopathology was reported as low differentiation adenocarcinoma.The immunohistochemistry of the tumor cells via liver biopsy showed:Villin,CDX-2 was positive,Glypican-3 was partial positive,CK7,CK20,AFP,Hepatocyte were all negative.The initial histopathology was reported as an AFP-producing rectum adenocarcinoma with liver metastasis,which was a rare disease.So far,only 17 reports,none has been reported in China.Then,we summarize the characteristic of the disease:diagnosed with hepatic metastasis,raised serum AFP and a poor outcome,in addition to primary symptoms.This kind of disease is highly malignant.