Clinicopathologic and prognostic significance of overexpression of her-2/neu and p53 oncoproteins in gastric carcinoma using tissue microarray

The aim of the study was to verify the frequency of the immunohistochemical overexpression of her-2/neu and p53 in gastric carcinoma and their relation to the other clinicopathological features and the impact on survival rates. A total of 93 patients of gastric carcinoma, who had a potential curative surgery in the period from 2001-2007 and with representative paraffin blocks, and sufficient follow-up data were included in this study. They were arrayed and evaluated for protein marker overexpression using tissue microarray [TMA]. Patients, tumor and treatment characteristics were collected from the patients files. The possible prognostic significance of p53 and her-2/neu over expression and different clinicopathological features on survival rates were explored. Twenty four [25.8%] cases were her-2/neu and p53 positive. None of the examined clinicopathologic factors had a significant relation to her-2/neu overexpression p53 was overexpressed in intestinal type, 14/34 [41.2%], more than in diffuse type, 10/59 [16.9%], [p= 0.01]. There was no relation between the overexpression of p53 and her-2/neu. The median survival period was 17.7 months. The survival rates at 12 months were 64.2%, 52.2%, 55.6% and 45.0% for overall [OS], local control [LC], metastasis free survival [MFS] and disease free survival [DPS] rates, respectively. Patients with advanced stages had a significantly lower OS and MFS. Age above 57 years was associated with significantly lower OS, LC, MFS and DPS. Patients who received radiotherapy had significantly higher OS, LC, MFS and DPS. None of the survival rates had been affected by the overexpression of p53, or her-2/neu. Although, this study failed to show any prognostic effect of p53 and her-2/neu on survival rates, we may suggest that p53 overexpression may play a role in the pathogenesis of intestinal gastric adenocarcinoma. It could also demonstrate the significantly improved survival rates with adjuvant chemoradiation. Also, TMA is a useful technique for rapid identification of protein expression profiles using minimal samples from archived tissues

HLA-DQA and DQB alleles and predisposition to insulin dependent diabetes mellitus

Type I insulin-dependent diabetes mellitus [IDDM] is an autoimmune disease. Onset of the disease is attributed to interplay between genetic and environmental risk factors. It is strongly associated with the presence of arginine in position 52 of DQ alpha [alpha] chain and the absence of aspartic acid in position 57 of the DQ beta [alpha] chain. In this study we assessed the relative contribution of DQ alpha and DQ alpha chains to susceptibility to type I diabetes among the Egyptian patients. We identified those genetically at risk of development among their siblings in order to detect early development of autoantibodies allowing early application of preventive programs. Genomic DNA of forty Egyptian type I IDDM patients, 13 non diabetic siblings and 22 non diabetic controls were amplified using polymerase chain reactionamplification refractory mutation system [ARMS] and genotyped for HLA-DQA and DQB alleles. A significant high frequency of homozygous genotype for DQB1 non- Asp allele was detected in patients 50%, p=0.01, odd ratio [OR] =10 at 95% confidence interval [CI] =2.1-48.6 with susceptible results to the disease. The frequency of diabetogenic heterodimer Arg/non-Asp was significantly high in patients [82%, p=0.044, OR= 3.26, at 95% CI= 1.005-10.6]. On the other hand, a significant lower frequency of homozygous genotype for DQB1 Asp allele was detected in patients 12.5%, p=0.065; it was associated with protection from the disease. In conclusion, in Egyptian patients susceptibility and protection from type I diabetes is mainly associated with the DQ alpha chain. Siblings have potential risk to the disease. Non affected siblings should be targeted in a larger study for counselling. At risk individuals should be subjected to regular monitoring for the early development of autoantibodies which start years before the overt diabetes.

2'-Deoxycytidine as a potential biomarker for detection of hepatocellular carcinoma

Background: 2'-deoxycytidine [Dcyd] is one of four major nucleosides found in the different normal body fluids due to dissolution of dead cells, and is increase in the presence of malignancy. Previous studies proved that it can be used as a marker for bladder cancer and acute lymphoblastic leukemia. The aim of this study is to assess 2'Dcyd as a possible biological marker in hepatocellular carcinoma [HCC]

Methods: four groups were evaluated for the level 2'-Dcyd as well as alpha-fetoprotein [AFP]; a control group [n = 20], 20 cases of chronic liver diseases [CLD], 20 cases of hepatitis C [HCV] 60 cases of HCC

Results: in the patients with HCC, 2'-Dcyd serum level was 8-fold higher than normal level. It was 3-fold higher in HCV group. A mild increase was noted in patients with chronic liver diseases. Levels >/= 0.14 of 2'-Dcyd had a sensitivity of 93% and specificity of 90% for diagnosis of HCC. It also recorded a sensitivity and specificity of 90% for diagnosis of HCV

Conclusions: for diagnosis of HCC, 2'-Dcyd is no better than AFP, as it is elevated in viral hepatitis C. A combination of AFP and 2'-Dcyd could provide broader information in diagnosis and treatment decision