Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatocellular carcinomas (HCCs) from 31 patients, cirrhotic livers from 7 patients and normal liver from 8 patients were immunohistochemically assessed in frozen sections using anti-P-glycoprotein (Pgp) monoclonal antibody C219. Immunohistochemical staining with anti-Ki-67 monoclonal antibody MIB-1 was performed for 22 HCCs to assess proliferative activity. Tumor tissues expressed Pgp on the biliary surface and on the luminal surface of cancer cells, which was less extensive than in normal and cirrhotic liver hepatocytes. Expression of Pgp was closely associated with the degree of histological differentiation and the histological type of HCC. Labeling indices (LI) of Pgp expression were 0.68 +/- 0.06 (mean +/- SD) in well, 0.51 +/- 0.14 in moderately and 0.04 +/- 0.06 in poorly differentiated HCC (significant differences among the three groups). LI of Pgp expression in the trabecular (0.55 +/- 0.15) and in the pseudoglandular types (0.44 +/- 0.10) were remarkably higher than in the compact type (0.04 +/- 0.06). The extent of Pgp expression in HCC was significantly inversely related to the extent of Ki-67 expression, in which Pgp expression decreased in highly proliferating tumors. In conclusion, Pgp expression in HCC was clearly related to its proliferative activity.
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PMID:Inverse relationship between P-glycoprotein expression and its proliferative activity in hepatocellular carcinoma. 914 5

Hepatocellular carcinoma (HCC) remains one of the most important malignancies in Japan (1, 2). Lactic dehydrogenase (LDH), which is a glycolyticenzyme, and exists in various types of human tissue and neoplasms, has also been reported to demonstrate a high level (especially LDH 5) in the serum of patients with HCC (3-10). We herein report the findings of a 68-year-old male patient with hepatocellular carcinoma (HCC), whose serum lactic dehydrogenase (LDH) level more closely correlated with the clinical course than the alpha-feto-protein level (AFP). Both the AFP and LDH levels were high before the operation (AFP 1402 ng/ml; LDH 638 IU/L) (LDH1 11%; LDH2 24%; LDH3 34%; LDH4 19%; LDH5 12%). The levels of the serum LDH and AFP one week after the right hepatic lobectomy both decreased to 423 IU/L and 331 ng/ml, respectively. In addition, the LDH isozyme pattern returned to normal. Six weeks after the operation, the serum LDH increased to 3504 IU/L, however, the AFP levels remained low at 43.4 ng/ml, and the CT findings demonstrated multiple recurrent nodules in the whole remnant liver. At eighty-one days after the operation, the patient died due to a rupture of the recurrent HCC. Immunohistochemical observations were performed using the peroxidase labeled streptavidin-biotin technique with slight modifications and using two monoclonal antibodies for AFP and for Ki-67. Most portions of the primary tumor consisted of poorly to undifferentiated HCC. The portion of undifferentiated HCC did not stain for AFP antibody, but the portion of poorly differentiated HCC stained positively for it. It was thus speculated that LDH was mainly produced in the portion of undifferentiated HCC. In addition the undifferentiated HCC were strongly positive for Ki-67, while, in contrast, the poorly HCC was only weakly positive for Ki-67. Based on the above findings, HCC with a high serum level of LDH appears to show both a rapid growth and highly malignant tumors.
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PMID:The characteristics of hepatocellular carcinoma with a high level of serum lactic dehydrogenase: a case report. 922 98

Large cell change (LCC), characterized by cellular enlargement, nuclear pleomorphism and hyperchromasia, and multinucleation of hepatocytes, is a common lesion in cirrhotic livers, but its nature, significance, and pathogenesis remain uncertain. Therefore, we assessed the prognostic value of LCC as a marker of subsequent hepatocellular carcinoma (HCC) through a case-control study that compared pretransplant liver biopsy specimens from 37 cirrhotic liver transplant recipients with HCC to specimens from a control group of recipients without HCC, matched for sex, age (+/-5 years), and cause of cirrhosis. LCC was identified in 16 (43%) of the study and 7 (19%) of the control group biopsy specimens. By matched-pair analysis, LCC conveyed a moderately increased risk of later HCC with an estimated odds ratio of 3.3 (95% CI, 1.2-15; P = .038). However, a pathology review of 45 HCCs showed adjoining LCC in only 12 (27%) and did not suggest a morphological transition or a histogenetic association between the two lesions. LCC hepatocytes displayed a low proliferative rate by Ki-67 or proliferating cell nuclear antigen immunostaining (labeling indices of 0.27 and 0.73) but showed a greater degree of apoptosis than normal hepatocytes (labeling indices of 1.9 and 0.23; P = .03) To reconcile these findings, we propose that LCC derives from derangements in the hepatocyte's normal process of polyploidization. Such derangements, possibly caused by chronic inflammation-induced DNA damage, could yield a population of enlarged liver cells with nuclear atypia and pleomorphism, frequent binuclearity, and minimal proliferation. According to this hypothesis, LCC would be a habitual feature of cirrhosis and a regular accompaniment of HCC but would not represent a direct malignant precursor.
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PMID:Large cell change (liver cell dysplasia) and hepatocellular carcinoma in cirrhosis: matched case-control study, pathological analysis, and pathogenetic hypothesis. 979 34

Metallothionein is the carrier protein of heavy metal ions, such as copper (Cu) and zinc (Zn). In this study, the relationships among immunohistochemical expression of metallothionein, concentrations of Cu and Zn, histological differentiation and proliferative activity of hepatocellular carcinoma were investigated in 51 cases. The concentrations of Cu and Zn in both tumor and non-tumor tissues were determined using electron probe microanalysis. Immunohistochemical expression of metallothionein in tumor tissues decreased with the degree of differentiation, whereas the number of hepatocytes positive for Ki-67 increased. Furthermore, the concentrations of Cu and Zn in tumor tissues decreased with the degree of histological differentiation in human hepatocellular carcinoma.
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PMID:Metallothionein expression and concentrations of copper and zinc are associated with tumor differentiation in hepatocellular carcinoma. 945 36

To clarify the relationship between angiogenesis and hepatocarcinogenesis on progression of hepatocellular carcinoma (HCC), we quantitatively evaluated angiogenesis by CD34 immunohistochemistry in liver cirrhosis (LC), adenomatous hyperplasia (AH), and HCC, and proliferative activity estimated by Ki-67 immunohistochemistry. Angiogenesis was evaluated by CD34 immunohistochemistry using monoclonal antibody HPCA-2, and tumor proliferative activity was evaluated using monoclonal antibody MIB-1. We used an image analysis system to assess the microvessel density as the area percentage of the endothelial area. Angiogenesis was generally observed in HCC and there was no significant difference among all clinical stages and histological grades of HCC. On the other hand, the staining of CD34 was partly observed in sinusoids of AH, although no positive staining was seen in any sinusoids of LC. The proliferative activity was significantly correlated with the clinical stage and histological grade of HCC. Our results indicate that the quantitation of angiogenesis does not provide significant prognostic information in HCC, but that it may have diagnostic value in distinguishing HCC from non-HCC. Meanwhile, AH, which is not morphologically diagnosed as cancer, shows positive staining for CD34, suggesting that some portion of AH contains cancerous characteristics.
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PMID:Angiogenesis in hepatocellular carcinoma as evaluated by CD34 immunohistochemistry. 954 62

Ki-67 expression in tumours has been shown to be associated with prognosis in patients with hepatocellular carcinoma (HCC). In this study, primary HCC samples were obtained from 67 patients undergoing surgical resection. None of these patients had been subjected previously to any other form of therapy, such as arterial embolization or chemotherapy. Histologically normal liver tissues from liver resection for metastatic colon cancer were taken as controls (n = 8). Monoclonal antibody against Ki-67 was used for immunostaining and flow cytometry was used to measure tumour DNA ploidy. The mean Ki-67 labelling index (percentage of Ki-67-positive cells) of the HCC (26 +/- 22%; range 0.1-89%) was significantly higher than that of the normal controls (39 +/- 0.8%, P < 0.05). The mean Ki-67 labelling index (19 +/- 15%; n = 28) of the tumours with diploid DNA pattern was significantly lower than those with aneuploid DNA pattern (32 +/- 25%, n = 39; P = 0.01). Hepatocellular carcinoma patients (n = 47) with Ki-67 index > 10% had a significantly lower disease-free and overall survival than those (n = 20) with Ki-67 index < or = 10% (P = 0.0009 and P = 0.02, respectively). Multivariate analysis showed that Ki-67 expression and tumour node metastasis stage were two independent prognostic factors for disease-free and overall survival rates. Our results suggest that the expression of Ki-67 is an independent prognostic indicator for patients with HCC after resection and could be of assistance in the decision-making of adjuvant therapy.
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PMID:Ki-67 expression as a prognostic marker in patients with hepatocellular carcinoma. 957 Feb 40

We investigated the role of apoptosis in relation to proliferative activity in hepatocellular carcinoma (HCC) using in situ DNA nick end labeling (ISNEL) and immunostaining for the Ki-67 antigen in 35 patients with HCC. We also performed immunostaining for Fas and Fas ligand (Fas L) to determine the relationship between the Fas system and apoptosis. The ratio of the ISNEL labeling index (LI) to the Ki-67 LI was significantly lower in HCC than in surrounding nontumorous liver tissue (p<0.0001), suggesting that a decrease in apoptosis relative to cell proliferation is important in the pathogenesis of HCC. Fas and Fas L were expressed in both HCC and nontumorous tissue, but Fas and Fas L LIs were significantly lower in HCC (p<0.0001). Fas expression by cells near ISNEL-positive cells tended to be increased in nontumorous tissue in mirror-image sections, suggesting that apoptosis is related to Fas expression. However, this pattern was rarely observed in HCC. These findings indicate that the Fas system may not play a major role in apoptosis in HCC.
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PMID:The Fas system is not significantly involved in apoptosis in human hepatocellular carcinoma. 958 70

Prognostic factors in hepatocellular carcinoma (HCC) conventionally consist of staging with the tumour node metastasis system and grading by tumour cellular differentiation. There are also other factors useful in prognostication but most of them are clinical. With new discoveries in the pathobiology of cancers and introduction of new medical technology, pathological and biological factors of HCC in relation to prognosis have been studied quite extensively. Morphological features of the tumour, both gross and histological, have been found to be significantly related to tumour recurrence and patient survival. Recently, applications of new antibodies and techniques have enabled studies on cellular proliferation using different antibodies such as those for proliferating cell nuclear antigen and Ki-67 protein. These studies on cellular proliferation, as well as assessment of argyrophilic nucleolar organizing regions, have been shown to provide good prognostic significance. Flow cytometric studies on DNA ploidy and studies on expression of genes including the p53 gene, hormone receptors and others show less unanimous results in their prognostic significance. The influence of gender on survival is also reviewed. In conclusion, pathological and biological factors are useful and help to guide clinicians in the management of patients and in assessment of long-term prognosis.
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PMID:Prognostic significance of pathological and biological factors in hepatocellular carcinoma. 971 14

It has been reported that hepatitis C virus-related hepatocellular carcinoma (HCC) patients survive longer than hepatitis B virus-related patients. In this study, since HCC patients positive for anti-HCV antibody had significantly longer disease-free survival (p<0.05), we evaluated the proliferative activity of 58 resected HCCs and the status of their viral infections. Ki-67 (MIB-1) immunostaining, argyrophilic nucleolar organizer regions and c-myc gene amplification were examined as parameters of proliferation, and p53 overexpression was examined in relation to clinicopathologic features and prognosis. Thirty-nine patients with HCC (67%) were positive for anti-HCV antibody alone, five (9%) were negative for both anti-HCV and HBV antibodies, two (3%) were positive for both anti-HCV and HBV antibodies, and 12 (21%) had HBsAg alone. HCC patients with anti-HCV antibody had a lower MIB-1 labeling index (LI) than HCC patients negative for the antibody (p<0.05), irrespective of the serum HBsAg status. However, there was no significant correlation between anti-HCV antibody and other proliferative parameters. MIB-1 could simply be related to cellular proliferation. On the other hand, the other parameters may be related to tumor progression as well as proliferation. HCV-related HCC does have lower proliferative activity and a better prognosis.
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PMID:Low MIB-1 labeling index in anti-HCV positive hepatocellular carcinoma. 977 94

In the development of a cancer, unlimited cell proliferation has been believed to play an important role. In addition, a programmed cell death called apoptosis, which is regulated by several oncogenes and tumor suppressor genes, has been suggested to be another important different pathway of carcinogenesis. Recently, several reports on cell proliferation capacity and apoptosis in the development of human liver disease have been published, but the cell proliferation index and its relationship between the expression of the bcl-2 and p53 genes involving apoptosis has not yet been discussed in view of the clinical differences of primary and metastatic liver cancer. In this study, we investigated the cell proliferation index and expression of p53 and bcl-2 in the tumorous and non-tumorous portions of both hepatocellular carcinoma and metastatic liver cancer. The expression of p53 was observed in both hepatocellular carcinoma and metastatic liver cancer, but bcl-2 expression was observed neither in hepatocellular carcinoma nor in metastatic liver cancer. In hepatocellular carcinoma, the p53 positive group showed a higher Ki-67 score (cell proliferation index) and more tumor numbers than the p53 negative group (p < 0.05). In metastatic liver cancer, the results were the same as in hepatocellular carcinoma (p < 0.05). However, we could not correlate the p53 expression and its prognostic significance in hepatocellular carcinoma.
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PMID:Cell proliferation index and the expression of p53 and Bcl-2 in tumorous and non-tumorous lesions of hepatocellular carcinoma and metastatic liver cancer. 982 91


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