ABSTRACT
BACKGROUND Gastric dysplasia (GD) is a precursor lesion of gastric adenocarcinoma. Intestinal type gastric carcinoma commonly shows microsatellite instability (MSI) and the diffuse type is associated with down regulation of E-cadherin. HER-2/neu is over-expressed in some cases of gastric cancer. In this study, MSI and expression rates of HER-2/neu and E-cadherin in GD were evaluated. METHODS Paraffin blocks of 21 cases of low grade dysplasia (LD), 11 cases of high grade dysplasia (HD) and 25 cases of indefinite for dysplasia (ID) were collected. After deparaffinization and antigen retrieval, the sections were incubated with antibodies against E-cadherin, hMLH1, hMSH2 and HER-2/neu. The streptavidin-biotin complex method was used followed by peroxidase enzyme development with diaminobenzidine. RESULTS HER-2/neu was positive in six cases of HD (50%), four LD (21%) and two ID (9%). E-cadherin was absent in two cases of LD and showed normal expression in all HD and ID cases. hMLH1 expression was absent or markedly decreased only in the zones of dysplasia in HD (3/11), LD (3/21) and ID (4/25). Absence or diminished expression of hMSH2 was seen in HD (3/11), LD (2/21) and ID (3/25) cases. HER-2/neu expression showed close association with diminished expression of hMLH1 or hMSH2 (p < 0.05). CONCLUSION Stepwise increase in the expression rate of HER-2/neu was seen in ID, LD and HD cases implying its role in cancer evolution. The absence of hMLH1 and hMSH2 in GD may predispose individuals to over-expression of other oncogenes such as HER-2/neu. Abnormal expression of E-cadherin is not a frequent finding in GD.
ABSTRACT
Atherosclerosis, and its most common manifestation, coronary artery disease (CAD), are rather common causes of morbidity and mortality worldwide. Recognition of its various risk factors is important to planning effective preventive measures. After the homocysteine theory was presented in 1969, attention has been directed toward the serum homocysteine level as a coronary artery disease risk factor. The authors aimed to assess the relationship between hyperhomocysteinemia and CAD in an Iranian population. In a case control study, 197 individuals (male: 123 [62.4%]) who were scheduled for coronary angiography were selected. Venous samples were taken from the patients in fasting state before angiography. Data about age, sex, risk factors (eg, hypertension, diabetes, smoking, hyperlipidemia, obesity) were obtained from prepared questionnaires. Homocysteine levels in patients were measured by ELISA method. A homocysteine level above 15 mumol/liter was considered high. Angiography reports and homocysteine levels were analyzed by independent sample t test, one-way ANOVA, multiple linear regression, and stratified analysis. In comparison with the patients with normal angiography reports (32.5%), patients with abnormal angiography reports (67.5%) had increased levels of homocysteine (p = 0.001). About 28.1% of patients with normal angiography reports had hyperhomocysteinemia. After further evaluation, linear correlations were detected between the numbers of involved vessels and homocysteine level (p = 0.000). Multiple linear regression analysis of data detected that in individuals without any risk factors, the relationship was stronger and more meaningful (p = 0.000). These data show that hyperhomocysteinemia is related to CAD as an independent risk factor. In individuals without any risk factors a linear correlation between homocysteine level and numbers of coronary artery involvement was present. If this equation is confirmed prospectively in other studies, the level of plasma homocysteine may he used as a noninvasive way of predicting the number of diseased coronary arteries.
