Double immunocytochemical staining for HBsAg and HBcAg in hepatocellular carcinoma and surrounding nontumorous liver tissue

Abstract Introduction: Epidermal growth factor receptor (EGFR) signaling plays an important role in various cancers, including hepatocellular carcinoma (HCC). We aimed to evaluate immunoexpression of EGFR in HCC and surrounding non-tumor liver tissue and to correlate it to multiple clinicopathologic data. Material and Methods: We analyzed 60 patients with HCC for multiple clinicopathologic characteristics and survival. Presence of the immunosignal and the percentage of positive tumor cells at the whole tumor tissue sample and adjacent cirrhotic liver tissue were semi-quantitatively determined. Results: Nineteen patients (31.67%) were female and 41 (68.33%) were male ranging in age from 31 to 85 years, median 61.88±10.51. Mean survival time for female patients was 8.86±1.76 months, for male 13.03±1.50 months and overall survival was 11.6051±1.19 months. The most patients had: T2 status (41.67%), no enlarged lymph nodes (90%), vascular invasion (63.33%) and well differentiated (43.33%) tumors. EGFR immunoexpression was determined in range from 0% to 100% in both tumor and non-tumor tissue with mean value of 39.58% in tumor and 86.86% in cirrhotic tissue (p<0.00). Higher percent of tumor EGFR positive cells were found in cases with higher T status, higher levels of AFP and poorly differentiated carcinoma, but not significantly. Lower percent of tumor EGFR positive cells were found in patients with vascular invasion and enlarged lymph nodes, but also not significantly. EGFR expression in tumor tissue significantly influenced survival of the patients (p<0.05). Conclusion: The study showed that expression of EGFR in lower percentage of tumor cells was associated to favorable prognosis, making it a potential prognostic marker and therapeutic target.

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Immunohistochemical detection of aflatoxin B1-DNA adducts and hepatitis B virus antigens in hepatocellular carcinoma and nontumorous liver tissue.

Environmental Health Perspectives ◽

10.1289/ehp.9399199 ◽

1993 ◽

Vol 99 ◽

pp. 199-202 ◽

Cited By ~ 1

Author(s):

R M Santella ◽

Y J Zhang ◽

C J Chen ◽

L L Hsieh ◽

C S Lee ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Dna Adducts ◽

Aflatoxin B1 ◽

Immunohistochemical Detection ◽

B Virus ◽

Hepatitis B Virus Antigens ◽

Virus Antigens ◽

Nontumorous Liver Tissue

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Treatment of hepatocellular carcinoma with octreotide: a randomised controlled study

Gut ◽

10.1136/gut.42.3.442 ◽

1998 ◽

Vol 42 (3) ◽

pp. 442-447 ◽

Cited By ~ 196

Author(s):

E Kouroumalis ◽

P Skordilis ◽

K Thermos ◽

A Vasilaki ◽

J Moschandrea ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Tissue ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Somatostatin Receptors ◽

Controlled Study ◽

Rank Test ◽

Somatostatin Analogue ◽

Advanced Hepatocellular Carcinoma ◽

Antimitotic Activity

Background—Standard treatment of inoperable hepatocellular carcinoma has not been established. Somatostatin has been shown to possess antimitotic activity against a variety of non-endocrine tumours.Aims—To assess the presence of somatostatin receptors in human liver and to treat advanced hepatocellular carcinoma with the somatostatin analogue, octreotide.Methods—Somatostatin receptors were measured in liver tissue homogenates from patients with acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Fifty eight patients with advanced hepatocellular carcinoma were randomised to receive either subcutaneous octreotide 250 μg twice daily, or no treatment. Groups were comparable with respect to age, sex, Okuda classification, presence of cirrhosis, and liver biochemistry and virology.Results—Various amounts of somatostatin receptors were identified in liver tissue of all patients including those with hepatocellular carcinoma. Treated patients had an increased median survival (13 months versus four months, p=0.002, log rank test) and an increased cumulative survival rate at six and 12 months (75% versus 37%, and 56% versus 13% respectively). Octreotide administration significantly reduced α fetoprotein levels at six months. When a multivariable Cox’s proportional hazards model was fitted, variables associated with increased survival were: treatment administration, absence of cirrhosis, increased serum albumin, and small tumours. Treated patients clearly had a lower hazard (0.383) in the multivariate analysis.Conclusions—Octreotide administration significantly improves survival and is a valuable alternative in the treatment of inoperable hepatocellular carcinoma.

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Quantitative Analysis of Aldolase A mRNA in Liver Discriminates between Hepatocellular Carcinoma and Cirrhosis

Clinical Chemistry ◽

10.1093/clinchem/46.7.901 ◽

2000 ◽

Vol 46 (7) ◽

pp. 901-906 ◽

Cited By ~ 24

Author(s):

Giuseppe Castaldo ◽

Giuseppe Calcagno ◽

Raffaella Sibillo ◽

Rosario Cuomo ◽

Gerardo Nardone ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Chronic Hepatitis ◽

Quantitative Analysis ◽

Hepatitis C ◽

Liver Tissue ◽

Liver Diseases ◽

Chronic Liver ◽

Chronic Liver Diseases ◽

Liver Biopsies ◽

Aldolase A

Abstract Background: Chronic liver diseases can progress to cirrhosis and to hepatocellular carcinoma. Timely and unequivocal recognition of the neoplastic evolution of cirrhosis is critical. To this aim, we used a noncompetitive reverse transcription-PCR procedure to analyze aldolase A mRNA in liver tissue from patients with chronic liver diseases at different stages. Methods: We studied 12 patients with hepatocellular carcinoma, 19 patients affected by chronic hepatitis C or cirrhosis, and 7 healthy controls. Aldolase A mRNA was reverse-transcribed to cDNA, which was then amplified by PCR. The amplified segments were “read” with a novel dot-blot procedure. A calibrator with the same sequence, synthesized in vitro using a T7 phage promoter, was processed at scalar dilutions in parallel to the target samples to generate a calibration curve and so quantify the target mRNA (detection limit, 0.03 amol; linearity spanning five orders of magnitude). Results: Aldolase A mRNA was ∼10-fold higher in liver biopsies from patients with hepatocellular carcinoma vs patients with chronic hepatitis C or cirrhosis, and healthy individuals. Furthermore, aldolase A mRNA concentrations were 1.2- to 21.3-fold higher in 12 liver biopsies compared with the paired surrounding cirrhotic tissue. Conclusions: The quantitative analysis of liver tissue aldolase A mRNA differentiates between nonneoplastic chronic liver diseases and hepatocellular carcinoma, which suggests that it has diagnostic potential.

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Phospholipids are A Potentially Important Source of Tissue Biomarkers for Hepatocellular Carcinoma: Results of a Pilot Study Involving Targeted Metabolomics

Diagnostics ◽

10.3390/diagnostics9040167 ◽

2019 ◽

Vol 9 (4) ◽

pp. 167

Author(s):

Erin B. Evangelista ◽

Sandi A. Kwee ◽

Miles M. Sato ◽

Lu Wang ◽

Christoph Rettenmeier ◽

...

Keyword(s):

Machine Learning ◽

Hepatocellular Carcinoma ◽

Fatty Acids ◽

Free Fatty Acids ◽

Small Molecules ◽

Bile Acids ◽

Random Forests ◽

Liver Tissue ◽

Classification Performance ◽

Tissue Biomarkers

Background: Hepatocellular carcinoma (HCC) pathogenesis involves the alteration of multiple liver-specific metabolic pathways. We systematically profiled cancer- and liver-related classes of metabolites in HCC and adjacent liver tissues and applied supervised machine learning to compare their potential yield for HCC biomarkers. Methods: Tumor and corresponding liver tissue samples were profiled as follows: Bile acids by ultra-performance liquid chromatography (LC) coupled to tandem mass spectrometry (MS), phospholipids by LC-MS/MS, and other small molecules including free fatty acids by gas chromatography—time of flight MS. The overall classification performance of metabolomic signatures derived by support vector machine (SVM) and random forests machine learning algorithms was then compared across classes of metabolite. Results: For each metabolite class, there was a plateau in classification performance with signatures of 10 metabolites. Phospholipid signatures consistently showed the highest discrimination for HCC followed by signatures derived from small molecules, free fatty acids, and bile acids with area under the receiver operating characteristic curve (AUC) values of 0.963, 0.934, 0.895, 0.695, respectively, for SVM-generated signatures comprised of 10 metabolites. Similar classification performance patterns were observed with signatures derived by random forests. Conclusion: Membrane phospholipids are a promising source of tissue biomarkers for discriminating between HCC tumor and liver tissue.

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Hypermethylation of MT1G and MT1H CpGs Promoter Sites and High Serum Levels of Cu Affect Survival Rate of Patients Affected by Hepatocellular Carcinoma

Current Developments in Nutrition ◽

10.1093/cdn/nzaa067_018 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 1791-1791

Author(s):

Domenica De Santis ◽

Silvia Udali ◽

Andrea Ruzzenente ◽

Greta Beschin ◽

Patrizia Pattini ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Dna Methylation ◽

Trace Elements ◽

Survival Rate ◽

Mortality Rate ◽

Liver Tissue ◽

Kaplan Meier ◽

Promoter Dna Methylation ◽

Promoter Dna

Abstract Objectives Recent evidences suggest a principal role of trace elements and metallothioneins (MTs), proteins involved in metal ions homeostasis and detoxification, in hepatocellular carcinogenesis. The study was designed to evaluate whether serum and liver tissue concentrations of the trace elements Cu, Zn and Se are implicated in survival rate of hepatocellular carcinoma (HCC) patients and if promoter DNA methylation is involved in trace elements-related proteins regulation. Methods Cu, Zn and Se levels were determined in serum and liver tissue samples, both HCC and homologous non neoplastic tissue (N) of 27 HCC patients by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Gene expression analysis of MT1G and MT1H, was performed by Real-time qPCR in HCC and N tissue. Promoter DNA methylation of a region overlapping MT1G and MT1H promoters was assessed by bisulfite amplicon sequencing (BSAS) in HCC and N tissues of 23 patients. Kaplan-Meier survival curves were drawn using the log-rank test (Mantel-Cox test) to examine the differences in survival according to serum trace elements and to gene-specific methylation levels. Results Kaplan-Meier analysis according to serum Cu levels showed that subjects within the highest quintile had an increased mortality rate (88.9%) compared with the other four quintiles (P = 0.025). Considering the 80th percentile of Cu levels (1118 μg/L), subjects with Cu concentrations above this value had a significantly decreased survival rate (P < 0.001). Se and Zn content were depleted in HCC tissues as compared to N tissues (P < 0.0001). MT1G and MT1H were strongly repressed in HCC tissues and precisely, MT1H in 24 out of 27 HCC tissues (P = 0.008) and MT1G in 23 out of 27 HCC tissues (P = 0.037). Nine out of 19 HCC tissues showing a down-regulation of MTs with three CpG sites, significantly hypermethylated in HCC tissue as compared to N tissue (P < 0.05). Considering the median methylation level, patients with higher methylation values showed increased mortality rate (P = 0.015). Conclusions The significant repression of MT1G and MT1H in HCC tissue is related to promoter hypermethylation and support the hypothesis of MT1G and MT1H as possible tumor suppressor genes in HCC. The evidence of promoter methylation levels and survival rate association provide new insights for the role of DNA methylation in liver carcinogenesis. Funding Sources N/A.

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