Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The great advances in radiological imaging techniques and their widespread availability have focused attention on hepatic premalignant nodular lesions. The histological differential diagnosis of these nodules can often be difficult, especially in needle biopsy specimens with limited material. Diagnostic considerations differ significantly between livers with and without cirrhosis: In the noncirrhotic liver, the differential diagnosis includes liver cell adenoma, nodular regenerative hyperplasia, and hepatocellular carcinoma. In cirrhosis, dysplastic nodules (low and high grade), dysplasia (large and small cell) as well as hepatocellular carcinoma may occur. The standardization and the uniform use of the nomenclature of these entities are necessary for a better understanding of the biological nature and etiopathology of these lesions. Only a commonly accepted nomenclature makes a comparison of different therapeutic treatment regimens feasible.
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PMID:[Preneoplasia of the liver. Definition--differential diagnosis--clinical consequences]. 1176 39

The effects of dose and duration of estrogen treatment on cholestasis, hepatic regeneration, and the genesis of liver tumors are evaluated in this work. Estrogens, especially at high doses during pregnancy or after long use of oral contraceptives (OCs), cause a constant diminution of bile secretion which remains subclinical in the great majority of cases. Ethinyl estradiol causes a constant but reversible cholestasis in the rat. 2 categories of cholestasis related to estrogens are distinguished in clinical practice; cholestasis induced by estrogens in pregnancy or in OCs, and cholestasis aggravated or revealed by estrogens, such as primitive biliary cirrhosis. Cholestasis induced by estrogens is dose-dependent, but few clinical data are available on this point. Experience has shown that a woman predisposed to cholestasis due to condition even with low-dose combined OCs. OCs are contraindicated for women genetically predisposed to cholestasis. Evidence has been found of an interaction between estrogen and DNA in the initiation of regenerative processes after experimental hepatectomy. 2 benign liver tumors, hepatic adenomas and focal nodular hyperplasias, have become more common with widespread diffusion of OCs. The role of estrogens in the genesis of hepatic adenomas is well established, but is more controversial with focul nodular hyperplasia. The appearance of low- dose OCs does not seem to have decreased the incidence of benign liver tumors. On the other hand, 2 series totalling 113 cases have demonstrated that the risk of adenoma increases significantly with the duration of treatment, and another study of 32 cases of focal nodular hyperplasia and 12 adenomas showed that most of the women had used OCs for more than 5 years. Both types of tumor carry risks of hemorrhagic accidents, and adenomas at least also carry carcinoma appears more significant in a country like Great Britain with a very low prevalence of such cancers. Benign liver tumors are very rare and should not affect prescription of OCs. A hepatobiliary sonogram should be obtained for women seeking OCs. A sonographic image of a tumor less than 5 cm in diameter with the characteristics of a benign tumor should prompt termination of OCs and reexamination in 4 weeks. If the tumor is over 5 cm in diameter the diagnosis should be confirmed by another technique. The nodular hyperplasias that are large, painful, and easily accessible. Recent epidemiologic studies suggest that the prevalence of asymptomatic lithiases is not very different in OC users and nonusers, but the frequency of complications leading to cholecystectomy is greater in women receiving longterm estrogen treatment. An asymptomatic lithiasis in a young OC user does not necessarily require termination of OCs.
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PMID:[Hepatic and biliary repercussions of estrogens: dose or duration of treatment effect]. 1231 61

Malignant transformation of liver cell adenoma and unequivocal hepatocellular carcinoma in resected liver cell adenomas are rare. We report two cases of liver cell adenoma with concomitant hepatocellular carcinoma. The first occurred in a 19-year-old male with an asymptomatic liver mass and was discovered incidentally. He had a history of nephrotic syndrome treated with oral prednisolone for 15 years. The second occurred in a 46-year-old female who was admitted due to right tubo-ovarian abscess. Computerized tomography scanning incidentally found a 10-cm liver mass in the right lobe. There was no history of oral contraceptive use. Both patients were negative for serum hepatitis B surface antigen and anti-hepatitis C virus antibody. Neither had cirrhosis. These two cases imply that malignant transformation of liver cell adenoma does occur, and that liver cell adenomas should be excised when malignant transformation is suspected.
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PMID:Liver cell adenoma with concomitant hepatocellular carcinoma: report of two cases. 1251 62

Triamterene is a potassium-sparing diuretic used in the treatment of edema associated with congestive heart failure, cirrhosis of the liver, and other diseases in which edema may occur. Toxicity and carcinogenicity studies were conducted by administering triamterene (greater than 99% pure) in feed to groups of male and female F344/N rats and B6C3F1 mice for 15 days, 13 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium and Chinese hamster ovary cells. 15-day Studies: Groups of five male and five female rats were fed diets containing 0, 1,000, 3,000, 10,000, 30,000, or 60,000 ppm triamterene. The diets containing 10,000 ppm or more were unpalatable, and feed consumption by the 3,000 ppm groups was reduced. Rats exposed to 1,000 or 3,000 ppm triamterene received approximate doses of 80 or 60 mg/kg body weight per day (males) or 70 or 50 mg/kg per day (females). One male rat and two female rats receiving 3,000 ppm died during the second week of the study. The final mean body weights of 3,000 ppm male and female rats were significantly lower than those of controls. Rats in the 3,000 ppm groups had renal tubule regeneration and cytoplasmic vacuolization of the zona glomerulosa of the adrenal gland. Groups of five male and five female mice were fed diets containing 0, 300, 1,000, 3,000, 10,000, or 30,000 ppm triamterene, but the diets containing 10,000 or 30,000 ppm were unpalatable. All mice receiving 3,000 ppm died by day 6. Mice exposed to 300 or 1,000 ppm triamterene received approximate doses of 40 or 155 mg/kg body weight per day (males) or 45 or 170 mg/kg body weight per day (females). The final mean body weights of mice in the 300 and 1,000 ppm groups were similar to those of the controls. Renal tubule degeneration and necrosis were observed in the kidney of 3,000 ppm mice. 13-Week Studies: Groups of 10 male and 10 female rats were fed diets containing 0, 150, 300, 600, 1,200, or 2,400 ppm triamterene. All rats receiving 2,400 ppm died before the end of the study; all other rats survived to the end of the study. Rats exposed to 150, 300, 600, or 1,200 ppm triamterene received approximate doses of 10, 20, 40, or 70 mg/kg body weight per day (males) or 10, 20, 40, or 80 mg/kg per day (females). Body weight gains and final mean body weights of rats in the 1,200 ppm groups were significantly lower than those of controls. There were no biologically significant differences in hematologic, clinical chemistry, or urinalysis parameters among exposed and control rats. Calculi were observed in the renal pelvis of four male rats in the 1,200 ppm group. Chemical-related lesions were observed in the kidney and adrenal gland of rats in the 1,200 and 2,400 ppm groups. These consisted of degeneration and regeneration of the renal tubule epithelium and cytoplasmic vacuolization of cells of the zona glomerulosa of the adrenal cortex. Depletion of hematopoietic cells from the bone marrow and of lymphocytes from the spleen and thymus of rats in the 2,400 ppm groups may have been related to debilitation and reduced feed consumption rather than chemical exposure. Groups of 10 male and 10 female mice were fed diets containing 0, 100, 200, 400, 800, or 1,600 ppm triamterene. All mice receiving 1,600 ppm, one 800 ppm female, one 200 ppm male, and four 100 ppm males died before the end of the study. Mice exposed to 100, 200, 400, or 800 ppm triamterene received approximate doses of 15, 25, 50, or 90 mg/kg body weight per day (males) or 15, 25, 50, or 115 mg/kg per day (females). The body weight gain and final mean body weight of male mice receiving 800 ppm were significantly lower than those of the controls. The total leukocyte and lymphocyte counts of males receiving 800 ppm and of females receiving 100, 400, or 800 ppm were significantly lower than those of controls. No other differences in hematologic, clinical chemistry, or urinalysis parameters were considered to be biologically significant. Necrosis of Lymphocytes was observed in the lymph node, spleen, and thymus of mice in the 800 and 1,600 ppm groups groups. 2-Year Studies: The doses selected for the 2-year studies were based on lower body weights, mortality, and chemical-related lesions observed in exposed animals during the 13-week studies. Groups of 70 male and 70 female rats were fed diets containing 0, 150, 300, or 600 ppm triamterene and groups of 70 male and 70 female mice were fed diets containing 0, 100, 200, or 400 ppm. Ten animals from each group were included for interim evaluations at 3 and 15 months. Because of a dosing error involving the high-dose mice at week 40, a second study was conducted with groups of 60 male and 60 female mice fed diets containing 0 or 400 ppm triamterene. In the 2-year studies, rats exposed to 150, 300, or 600 ppm triamterene received approximately 5,10, or 25 mg/kg body weight per day (males) and 5, 15, or 30 mg/kg (females) and mice exposed to 100, 200, or 400 ppm received approximately 10, 25, or 45 mg/kg (males) and 15, 30, or 60 mg/kg (females) per day. 3-Month and 15-Month Interim Evaluations in the 2-Year Studies: There were no biologically significant differences in hematologic, clinical chemistry, or urinalysis parameters between exposed and control rats or mice at the 3- or 15-month interim evaluations. At necropsy, the mean body weights of exposed rats and mice were similar to those of the controls. There were no chemical-related lesions in exposed rats at 3 months or in exposed mice at 3 or 15 months. At the 15-month evaluation, basophilic, clear cell, and mixed cell foci of the liver occurred in exposed male rats. No chemical-related lesions were observed in female rats at 15 months. Survival, Body Weights, Clinical Findings, and Feed Consumption in the 2-Year Studies: Survival of exposed rats was similar to that of controls (males: 0 ppm, 25/47; 150 ppm, 25/50; 300 ppm, 19/50; 600 ppm, 27/50; females: 29/50, 34/50, 34/50, 29/50). The mean body weights of 600 ppm rats were consistently lower than, but within 5% of, those of controls after week 49. Feed consumption by male and female rats was similar among exposed and control groups throughout the studies. There were no clinical findings of toxicity. Survival of 400 ppm male mice in the first study was lower than that of controls because of the dosing accident at week 40. Survival of 100 and 200 ppm male mice and of all exposed groups of female mice in the first study and of exposed males and females in the second study was similar to controls (males: first study, 0 ppm, 47/50; 100 ppm, 45/50; 200 ppm, 46/50; 400 ppm, 46/60; second study, 0 ppm, 43/50; 400 ppm, 39/50; females: first study, 38/50; 43/50; 43/50; 43/60; second study, 40/50; 38/51). Mean body weights of exposed mice were similar to those of controls throughout the first study with one exception; in the week following the dosing error, the mean body weight of 400 ppm males was 16% lower than that of controls. In the second study, mean body weights of 400 ppm mice were slightly lower than those of controls during the final 8 weeks. Feed consumption by exposed mice was similar to that by controls throughout the studies. There were no clinical findings of toxicity in exposed mice. Neoplasms and Nonneoplastic Lesions in the 2-Year Studies: The incidences of mixed cell foci and focal hyperplasia of the liver were significantly increased in 300 and 600 ppm male rats, and the incidences of clear cell and mixed cell foci were significantly increased in 300 and 600 ppm female rats. Hepatocellular adenomas occurred in all groups of exposed male rats, but none occurred in controls; the incidence of hepatocellular adenoma in the 150 ppm males was significantly higher than that of controls (O ppm, 0/50; 150 ppm, 6/50; 300 ppm, 4/50; 600 ppm, 3/49). Hepatocellular adenomas were observed in two 600 ppm female rats, but not in the lower exposure groups or in controls. No hepatocellular carcinomas were seen in exposed or control rats. The incidences of nephropathy in exposed rats were similar to those of controls, but the average severity of the lesion was marginally increased in male rats receiving 300 ppm and in female rats receiving 600 ppm (males: 47/50, 2.4; 49/50, 2.7; 50/50, 3.0; 49/50, 2.8; females: 38/50, 1.1; 45/50, 1.2; 45/50, 1.3; 45/50, 1.4). Although in the first study the incidences of hepatocellular adenoma in exposed male mice were similar to that of controls, the incidences of multiple adenomas were greater in the exposed groups, and the incidence of hepatocellular carcinoma in the 400 ppm group was marginally greater (hepatocellular adenoma: 0 ppm, 17/50; 100 ppm, 22/50; 200 ppm, 19/50; 400 ppm, 20/60; hepatocellular carcinoma: 5/50; 7/50; 3/50; 13/60). In the second study, the incidence of hepatocellular adenoma in the 400 ppm males was significantly higher than that of controls (hepatocellular adenoma: 0 ppm, 21/50; 400 ppm, 36/50; hepatocellular carcinoma: 9/50; 11/50). The incidences of hepatocellular adenoma in exposed female mice in the first and second studies were significantly greater than those of controls (hepatocellular adenoma, first study: 10/50; 22/50; 23/50; 36/60; second study: 7/50; 28/51). The incidences of multiple adenoma were also increased in the exposed groups. Although the incidences of hepatocellular carcinoma were similar among exposed and control female mice in the first study, the incidence of hepatocellular carcinoma in the 400 ppm females in the second study was marginally greater than that of controls (hepatocellular carcinoma, first study: 4/50; 4/50; 3/50; 8/60; second study: 5/50; 11/50). In both studies, hepatocellular foci (basophilic, eosinophilic, clear cell, or mixed cell) also occurred more frequently in exposed female mice than in controls. The incidences of thyroid gland follicular cell hyperplasia in the 200 and 400 ppm males and in all exposed groups of females were significantly greater than those of controls in the first study. These findings were confirmed in the second study (follicular cell hyperplasia: males, first study, 3/50, 8/50, 16/50, 20/60; second study, 0/50,16/50; females, first study, 4/49,17/49,18/50, 28/60; second study, 9/50, 32/51). The incidences of follicular cell neoplasms were similar among exposed and control mice in both studies. The incidences (28/50, 36/50, 43/50, 49/60) and average severity (0.56, 0.80, 1.00, 1.07) of nephropathy were marginally higher in exposed female mice than in controls in the first study. In the second study, the differences in incidence (15/50, 21/50) and severity (0.38, 0.55) were not as great. It is uncertain if these increases were related to the ingestion of triamterene. The incidences and severity of nephropathy were similar among exposed and control male mice in both studies. Genetic Toxicology: Triamterene was not mutagenic in Salmonella typhimurium strains TA98, TA100, TA1535, or TA1537 with or without exogenous metabolic activation (S9). It did not induce chromosomal aberrations in Chinese hamster ovary cells, with or without S9. Positive results were obtained for induction of sister chromatid exchanges in Chinese hamster ovary cells with and without S9. Conclusions: Under the conditions of these 2-year feed studies, there was equivocal evidence of carcinogenic activity of triamterene in male F344/N rats based on a marginal increase in the incidence of hepatocellular adenoma. There was no evidence of carcinogenic activity of triamterene in female F344/N rats administered 150, 300, or 600 ppm. There was some evidence of carcinogenic activity of triamterene in male B6C3F1 mice based on a marginal increase in the incidence of hepatocellular carcinoma in the first study and a significantly increased incidence of hepatocellular adenoma in the second study. There was some evidence of carcinogenic activity of triamterene in female B6C3F1 mice based on significantly increased incidences of hepatocellular adenoma and of adenoma and carcinoma (combined). Exposure to triamterene was associated with an increased incidence of hepatocellular foci, primarily mixed cell type, and an increase in the severity of nephropathy in female rats. In mice, exposure to triamterene was associated with an increased incidence of hepatocellular foci in females and an increased incidence of thyroid gland follicular cell hyperplasia in males and females. Synonyms: 6-Phenyl-2,4,7-pteridinetnamine; 6-phenyl-2,4,7-triaminopteridine; 2,4,7-triamino-6-phenypteridine; ademin; pterofen; pterophane; NSC-77625; SKF 8542 Trade names: Dyrenium, Dyazide, Dyren, Dytac, Jatropur, Maxzide, Noridyl, Triteren, Teriam, Urocaudal
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PMID:NTP Toxicology and Carcinogenesis Studies of Triamterene (CAS No. 396-01-0) in F344/N Rats and B6C3F1 Mice (Feed Studies). 1261 91

Aberrant promoter methylation is a fundamental mechanism of inactivation of tumor suppressor genes in cancer. The Ras association domain family 1A gene (RASSF1A) is frequently epigenetically silenced in several types of human solid tumors. In this study, we have investigated the expression and methylation status of the RASSF1A gene in hepatocellular carcinoma (HCC). In two HCC cell lines (HepG2 and Hep3B) RASSF1A was inactivated and treatment of these cell lines with a DNA methylation inhibitor reactivated the transcription of RASSF1A. The methylation status of the RASSF1A promoter region was analysed in 26 primary liver tissues including HCC, hepatocellular adenoma (HCA), liver fibrosis, hepatocirrhosis. Out of 15, 14 (93%) HCC were methylated at the RASSF1A CpG island and hypermethylation was independent of hepatitis virus infection. RASSF1A was also methylated in two out of two fibrosis and in three (75%) out of four cirrhosis; the latter carries an increased risk of developing HCC. Additionally, we analysed the methylation status of p16(INK4a) and other cancer-related genes in the same liver tumors. Aberrant methylation in the HCC samples was detected in 71% of samples for p16, 25% for TIMP3, 17% for PTEN, 13% for CDH1, and 7% for RARbeta2. In conclusion, our results demonstrate that RASSF1A and p16(INK4a) inactivation by methylation are frequent events in hepatocellular carcinoma, but not in HCA, which is in contrast to HCC without cirrhosis, viral hepatitis, storage diseases, or genetic background. Therefore, this study gives additional evidence against a progression of adenoma to carcinoma in the liver. Thus, RASSF1A hypermethylation could be useful as a marker of malignancy and to distinguish between the distinct forms of highly differentiated liver neoplasm.
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PMID:Frequent epigenetic inactivation of the RASSF1A gene in hepatocellular carcinoma. 1266 Aug 22

More procedures used in transection of the liver parenchyma include also resection by means of a harmonious scalpel with an enhanced haemostatic effect. Based on analysis of 51 patients operated on account of liver disease using a harmonious scalpel, the authors evaluate its asset to the liver resection technique. The harmonious scalpel was used in transection of the liver in seven patients with benign liver disease (inborn cysts, follicular nodular hyperplasia, haemangioma, hepatocellular adenoma) and in 44 with malignant disease (hepatocellular carcinoma, metastases, most frequently, i.e. 34x of colorectal carcinoma). Anatomical liver resection (hemihepatectomy, lateral bisegmentectomy, segmentectomy) was implemented in 34 patients, and in 17 a wedge-shaped resection. Transection of the parenchyma by a harmonious scalpel was made using 10 mm coagulation scissors, i.e. their blunt blade with a lower oscillation grade. The preoperative blood loss was from 30 to 300 ml. As to postoperative complications 2 patients developed cholascos, 2 fluidothorax, 1 respiratory failure and 2 early infection. Liver resection by means of a harmonious scalpel is a new method of parenchyma transection with adherence to the resection line without damage of the deeper structures, reducing preoperative haemorrhage and minimalizing the extent of resection in liver diseases with impaired regeneration of the parenchyma (cirrhosis). Liver transection by a harmonious scalpel is a safe method where it is essential to respect recommended technical parameters, incl. the necessary time.
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PMID:[Liver transection with the harmonic scalpel in elective liver surgery]. 1266 83

In surgical pathology, focal nodular hyperplasia (FNH) is sometimes difficult to diagnose, and liver cirrhosis (LC) and hepatocellular adenoma (HA) are often among the differential diagnoses. Recently, we found a reduced expression of angiotensin I-converting enzyme (CD143) in FNH compared with cirrhotic and noncirrhotic liver. Intrigued by this observation, we investigated the expression pattern of CD143 in FNH, LC, and HA and its possible diagnostic value. The expression of CD143 was studied by immunohistochemistry in 20 FNHs, 13 corresponding extralesional noncirrhotic liver parenchyma, 20 patients with LC, and four HAs. Endothelial cells were identified with antibodies directed against CD31 and CD34. CD31+, CD34+, and CD143+ sinusoidal endothelial cells were found in extralesional liver, LC, HA, and FNH. However, the number of CD143+ sinusoidal endothelial cells and the intensity of immunostaining were significantly reduced in FNH compared with extralesional liver, LC, and HA. The expression of CD143 was further assessed using a numerical scoring system ranging from 0 to 6. The mean immunoreactivity score for CD143 was 2.4 +/- 1.7 for sinusoidal endothelial cells in FNH, 5.7 +/- 0.6 in extralesional liver, 4.8 +/- 1.1 in LC, and 5.8 +/- 0.5 in HA. The differences between the mean immunoreactivity scores for CD143 were highly significant. The difference between FNH and extralesional liver was confirmed on transcriptional level by fluorescence-mediated real-time RT-PCR, which also showed a significantly decreased level of CD143 mRNA in FNH. Our study provides evidence that CD143 is down-regulated in FNHs and that the phenotype of endothelial cells lining the sinusoids in FNH differs from those in non-neoplastic liver, LC, and HA. The observed variations in expression patterns for CD143 might be of diagnostic use in surgical pathology.
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PMID:Angiotensin I-converting enzyme (CD143) is down-regulated in focal nodular hyperplasia of the liver. 1470 68

Distinguishing well-differentiated hepatocellular carcinoma (HCC) from benign hepatic lesions is challenging for pathologists in limited diagnostic material such as needle-core tissue biopsy and fine-needle aspiration (FNA) biopsy. The objective of this study is to test a hypothesis that the fortification of liver by reticulin along single cell plates should protect benign hepatic lesions from breakdown by the force of aspiration and smearing, whereas the decreased reticulin in well-differentiated HCC would result in finely granular FNA smear. The study involved FNA biopsies of 67 cases of well-differentiated HCC and 109 cases of benign hepatic lesions, including cirrhosis (22), liver cell adenoma (8), steatosis (7), focal nodular hyperplasia (6), liver with cholestasis (6), and unremarkable liver sampled from nodular hepatic lesions consistent with the regenerative nodules (60). A slide with the most sample from each case by gross inspection was mixed together. Two observers blinded to the diagnoses were asked to separate the slides into two groups based on smear characteristics by gross inspection. Fragments of rigid fine-needle cores was present in 109 out of 109 cases of benign hepatic lesions but absent in 61 out of 67 cases of well-differentiated HCC, which presented as finely granular smears. The difference is statistically significant. (P<0.001, df=1, chi2=149.3). Using the physical characteristic of liver aspirates as the screening test for malignancy, the sensitivity is 91%, specificity is 100%, positive predictive value is 100%, negative predictive value is 94.8%, and efficiency is 96.6%. In conclusion, the smear characteristics of liver samples in FNA biopsy correlate to their reticulin status on histology. This physical characteristic can be used as the first clue to distinguish malignant and benign liver aspirates prior to microscopic examination.
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PMID:Distinguishing well-differentiated hepatocellular carcinoma from benign liver by the physical features of fine-needle aspirates. 1504 22

Expression profiling of hepatocellular carcinoma has demonstrated that glypican 3 (GPC3), a heparan sulfate proteoglycan anchored to the membrane, is expressed at a markedly elevated level in hepatocellular carcinoma. In this paper, two monoclonal antibodies against GPC3, GPC3-C02 and A1836A, were confirmed to specifically recognize GPC3 molecule in cells from hepatocellular carcinoma and hepatoblastoma cell lines by immunoblotting, and both were confirmed to recognize different epitopes of the GPC3 molecule by epitope mapping. Then, we evaluated the feasibility of GPC3-immunohistochemistry in the pathological diagnosis of benign and malignant hepatocellular lesions by applying these monoclonal antibodies to formalin-fixed and paraffin-embedded specimens. The immunoreactivity turned out to be identical in the two monoclonal antibodies and was thus confirmed to represent the actual expression of the GPC3 molecule. The expression was observed in the fetal liver, but not in normal adult liver, liver cirrhosis or hepatitis except for a tiny focus of a regenerative nodule of fulminant hepatitis. Diffusely positive staining of GPC3 was observed in malignant hepatocytes in hepatoblastomas and in hepatocellular carcinomas (47/56, 84%). GPC3 expression was independent of the differentiation and size of the hepatocellular carcinoma. On the other hand, there was only weak and focal staining in low-grade (2/8) and high-grade dysplastic nodules (6/8). GPC3 immunoreactivity was detected in only one of 23 metastatic lesions of colorectal carcinoma, and its expression was entirely absent in the liver cell adenoma (0/7), carcinoid tumor (0/1), and cholangiocellular carcinoma (0/16). When compared with immunohistochemistry of hepatocyte antigen and alpha-fetoprotein, GPC3-immunohistochemistry was significantly much more specific and sensitive for hepatocellular carcinomas. Thus, GPC3 was confirmed to be one of the oncofetal proteins now attracting attention for their promise both as markers of hepatocellular carcinoma in routine histological examination and as targets in monoclonal antibody-based hepatocellular carcinoma therapy.
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PMID:The glypican 3 oncofetal protein is a promising diagnostic marker for hepatocellular carcinoma. 1592 May 46

The clinical and morphological definition of hepatocellular carcinoma (HCC), dysplasia and adenoma suffers from a lack of biological understanding. This is especially important in the histomorphological diagnosis of nodular liver lesions in needle biopsies. Therefore, we constructed a liver tissue micro-array (TMA) and evaluated 48 HCCs, 46 dysplasias, 8 adenomas, 20 cirrhotic specimens and 28 normal liver samples derived from 68 patients. Protein (over)expression by tumor suppressor genes p16, p53 and Rb1 was assessed by immunohistochemistry, the proliferative capacity was examined by immunostaining of Ki67. Further, DNA ploidy status (hyperdiploidy) was measured by fluorescent in situ hybridization (FISH) with a chromosome 1-specific repetitive DNA probe. An abnormal chromosome 1 number, i.e. the percentage of hyperdiploid cells, was 11.0, 13.7, 16.1, 23.7 and 31.3 for normal liver samples, adenomas, cirrhosis, dysplasias and HCCs, respectively. A significant difference was found for HCC versus cirrhosis (P = 0.024) or adenoma (P = 0.033), a trend (borderline significance) was seen for dysplasia versus cirrhosis (P = 0.094). Immunohistochemical protein localisation of p53 and Rb1, as well as Ki67 indicating proliferation, was clearly higher in HCC than in cirrhosis or dysplasia (all P < 0.001). Proliferation was also higher in HCC than in adenoma (P = 0.025), whereas a trend (borderline significance) was observed for Rb1 overexpression (P = 0.063). These data suggest that in the liver cell dysplasia-carcinoma pathway, changes in ploidy are followed by increased proliferation and cell biological perturbations involving p53 and Rb1. Adenomas can be distinguished from carcinomas, but not from dysplasias, based on ploidy and proliferation characteristics.
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PMID:Cell biological evaluation of liver cell carcinoma, dysplasia and adenoma by tissue micro-array analysis. 1600 Feb 13


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