Ola Nada

Pilot survey of aflatoxin–albumin adducts in sera from Egypt

Aflatoxins are potent liver carcinogens that frequently contaminate cereals in developing countries. Aflatoxin exposure has been predicted in Egypt but, to date, no studies have measured the level of aflatoxin–albumin (AF–alb) adducts as a validated biomarker to assess exposure. In this pilot survey, a limited number of sera samples, available from a hepatocellular carcinoma (HCC) case-control study in Egypt, were analysed. AF–alb was detected in 24/24 samples from HCC-negative individuals (geometric mean 9.0 pg mg−1; range 3.5–25.8pg mg−1), while 7/22 samples from HCC-positive cases had detectable AF–alb (geometric mean 2.6 pg mg−1; range: non-detectable–32.8 pg mg−1). These AF–alb data do not represent a case-control comparison due to inherent difficulties in comparing markers of dietary intake between controls and patients with disease. Although these data are limited, the potential health consequences of aflatoxin exposure in this region merit further investigation.

Immunohistochemical Detection of Hepatitis C Virus (Genotype 4) in B-cell NHL in an Egyptian Population: Correlation With Serum HCV-RNA

Background and AimRetrospective evaluation of hepatitis C virus (HCV) prevalence in lymphoma tissues has important applications in clarifying the contribution of viral factors to the pathogenesis. Trials for detection of HCV at the cellular level in lymphoma tissues are, so far, minimal with unsatisfactory results. We aimed to study the detection and localization of HCV in the tissues of B-cell non-Hodgkin lymphoma (NHL) patients. DesignWe performed immunohistochemistry to detect the HCV nonstructural 3 protein in paraffin-embedded tissue specimens of B-cell NHL patients, in 39 serum HCV-RNA positive samples and 35 serum HCV-RNA negative samples as controls. The serum analysis was carried out for HCV antibodies using enzyme-linked immunoassay and for HCV-RNA using reverse transcription-polymerase chain reaction. Reverse transcription-polymerase chain reaction was used to detect the HCV-RNA in tissues in immunohistochemically positive cases. We correlated the results with the clinicopathologic characteristics of the patients. ResultsA diffuse cytoplasmic immunohistochemical staining for HCV in the lymphoid cells was detected in 8 of 39 serum positive cases (20.5%), all of which were genotype 4, which is the most prevalent HCV genotype in Egypt. Only 2 out of 35 serum negative control samples showed positive staining and in 1 of them HCV-RNA was detected in tissue. No significant correlation was detected between HCV positive cases and the clinicopathologic features of the patients. ConclusionsImmunohistochemical detection of HCV proteins in lymphoma tissues supports a potential role of viral replication in lymphomagenesis. The low number of cases showing expression of viral proteins may represent a low viral load in lymphoid tissue and/or restriction of HCV protein expression to certain subtypes of B-cell NHL. Immunohistochemistry can be used as a complementary tool for specific HCV detection in the paraffin-embedded material of lymphoma tissues not suitable for RNA analysis.

Prognostic significance of HLA EMR8-5 immunohistochemically analyzed expression in osteosarcoma

BackgroundDefects in Human Leukocyte Antigen (HLA) class I antigen expression and/or function in tumor cells have been extensively investigated, because of their potential role in the escape of tumor cells from T cell recognition and destruction. The researchers evaluated HLA class I expression in tumor tissue as a prognostic factor in osteosarcoma patients and as a predictor of their survival. This retrospective cohort study was conducted at the pathology laboratory of Ain Shams University Hospital, and Ain Shams University Specialized Hospital during the period between January 2009 and January 2012.MethodsThe researchers investigated HLA class I expression in primary osteosarcoma by immunohistochemistry using EMR8-5 mAbs. Furthermore, researchers evaluated the correlation between HLA class I expression and the clinicopathological status and outcome in formalin fixed paraffin embedded tissues from thirty six (36) patients with osteosarcoma.ResultsA high expression of HLA class I was detected in 18 (50) % of tumor samples examined; while tumors with low or negative expression represented 9 (25%) cases each. Data indicate that the overall survival rate of patients with tumors highly expressing HLA class I was significantly higher than those with low or negative expression.ConclusionDown-regulation of class I antigen expression is associated with features of aggressive disease and a poorer prognosis. Therefore, it is imperative to identify HLA as a prognostic factor at the time of diagnosis to detect chemotherapy-resistant tumors and to generate a modified treatment regimen.Virtual slidesThe virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1159334857109547.

Implication of protein kinase R Gene quantification in hepatitis C Virus Genotype 4 induced Hepatocarcinogenesis

BackgroundProtein kinase RNA (PKR-regulated) is a double-stranded RNA activated protein kinase whose expression is induced by interferon. The role of PKR in cell growth regulation is controversial, with some studies supporting a tumour suppressor function and others suggesting a growth-promoting role. However, it is possible that the function of PKR varies with the type of cancer in question.MethodsWe report here a detailed study to evaluate the function of PKR in hepatitis C virus genotype 4 (HCV-4) infected patients. PKR gene was quantitated in HCV related malignant and non-malignant liver tissue by RT-PCR technique and the association of HCV core and PKR was assessed.ResultsIf PKR functions as a tumour suppressor in this system, its expression would be higher in chronic hepatitis tissues. On the contrary our study demonstrated the specific association of HCV-4 with PKR expressed in hepatocellular carcinoma (HCC) tissues, leading to an increased gene expression of the kinase in comparison to chronic hepatitis tissues. This calls into question its role as a tumour suppressor and suggests a positive regulatory role of PKR in growth control of liver cancer cells. One limitation of most of other studies is that they measure the levels rather than the quantitation of PKR gene.ConclusionThe findings suggest that PKR exerts a positive role in cell growth control of HCV-4 related HCC, obtaining a cut-off value for PKR expression in liver tissue provides the first evidence for existence of a viral activator of PKR.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1267826959682402.

Immunohistochemical expression of mismatch repair genes (hMSH2 and hMLH1) in hepatocellular carcinoma in Egypt

Helal TEA, Khamis NS, El‐Sharkawy TM, Nada OH, Radwan NA. Immunohistochemical expression of mismatch repair genes (hMSH2 and hMLH1) in hepatocellular carcinoma in Egypt. APMIS 2010; 118: 934–40.

Effectiveness of ravidasvir plus sofosbuvir in interferon-naïve and treated patients with chronic hepatitis C genotype-4

BACKGROUND & AIMS Although treatment of hepatitis C virus (HCV) and HCV-genotype-4 (GT4) has become very effective, it remains very expensive, and affordable options are needed, especially in limited resource countries. The aim of this study was to assess the efficacy and safety of the combination of ravidasvir (an NS5A inhibitor) and sofosbuvir to treat patients with chronic HCV-GT4 infection. METHODS A total of 300 patients with HCV-GT4 infection were recruited in three groups: treatment-naïve patients with or without compensated Child-A cirrhosis (Group 1); interferon-experienced patients without cirrhosis (Group 2); and interferon-experienced patients with cirrhosis (Group 3). Groups 1 and 2 received ravidasvir 200 mg QD plus sofosbuvir 400 mg QD for 12 weeks and were randomized 1:1 to treatment with or without weight-based ribavirin. Group 3 patients received ravidasvir plus sofosbuvir with ribavirin and were randomized 1:1 to a treatment duration of 12 weeks or 16 weeks. The primary endpoint was sustained virologic response at 12 weeks post-treatment (SVR12). RESULTS A total of 298 patients were enrolled: 149 in Group 1, 79 in Group 2 and 70 in Group 3. SVR12 was achieved in 95.3% of all patients who started the study, including 98% of patients without cirrhosis and 91% of patients with cirrhosis, whether treatment-naïve or interferon-experienced. Ribavirin intake and history of previous interferon therapy did not affect SVR12 rates. No virologic breakthroughs were observed and the study treatment was well tolerated. CONCLUSIONS Treatment with ravidasvir plus sofosbuvir, with or without ribavirin, was well tolerated and associated with high sustained virologic response rate for HCV-GT4 infected patients with and without cirrhosis, regardless of previous interferon-based treatments. TRIAL REGISTRATION NUMBER ClinicalTrials.gov Identifier: NCT02371408. LAY SUMMARY This study evaluated efficacy and safety of the new oral hepatitis C drug ravidasvir in combination with the approved oral drug sofosbuvir in 298 patients infected with hepatitis C type 4. Our results showed that treatment with ravidasvir plus sofosbuvir, with or without ribavirin, was well tolerated and associated with high response rate in patients with and without cirrhosis.

Immunohistochemical expression of stem cell markers CD133 and Oct4 in colorectal adenocarcinoma

Introduction Colon cancer is a deadly disease affecting millions of people worldwide. The cancer stem cell (CSC) concept has been proposed as an attractive theory to explain cancer development and is considered as target for the development of diagnostics and therapeutics. Colon CSCs may drive carcinogenesis by their tumor initiation and maintenance capabilities, thus accounting for chemotherapeutic failure. Although many CSC markers have been proposed, there is neither complete agreement with regard to them, nor has their presence in the early phases of carcinogenesis been established. We evaluated the immunohistochemical expression of stem cell markers CD133 and Oct4 using the avidin–biotin immunoperoxidase technique to investigate their clinical importance in the initiation and progression of colorectal cancer. Results CD133 immunostaining was higher in nonmetastatic tumors, suggesting the loss of its character in advanced metastatic lesions. Oct4 was overexpressed in malignant tumor cells compared with normal colonic epithelium and was also expressed more in late Duke stages and metastatic tumors. In conclusion, we show that Oct4 may play a role in colorectal adenocarcinoma development and progression, and we suggest its utilization as a significant prognostic marker in colorectal carcinoma patients.