Gallbladder carcinoma is the fi fth most common malignancy of the gastrointestinal tract. e absolute characteristics of the disease are the high mortality rate due to the late discovery of a tumor and the low therapeutic possibilities except by surgical intervention. In oncology we can predict the outcome of the disease with a combination of classical standard clinico/pathological parameters (stage of the tumors, diff erentiation) and the intrinsic genetic and biochemical properties of the tumor. Such intrinzic properties of the tumors that are connected with the outcome of the disease are the denominators (markers). e author searched extensively for the expression and infl uence of markers included in chronic infl ammation and early carcinogenesis, cell cycle regulation and tissue hypoxia: cyclooxygenase- (COX-), p gene and glucose transporter- protein (GLUT-). e author discusses their possible role in the development as well as fi ghting this disease, if specifi c medications targeting them were available.
The significant differences in COX-2 expression among normal epithelium, low-grade dysplasia and high-grade dysplasia suggest that overexpression of COX-2 enzyme is an early event in gallbladder carcinogenensis. Furthermore, since accumulation of p53 correlates with COX-2 expression, COX-2 overexpression observed in gallbladder high-grade dysplasia and carcinoma might be partly due to the dysfunction of p53.
GLUT-1 is a transmembrane glucose transport protein that allows the facilitated transport of glucose into cells, normally expressed in tissues which depend mainly on glucose metabolism. Enhanced expression of GLUT-1 can also be found in a large spectrum of carcinomas. This study aimed to investigate GLUT-1 expression in gallbladder tissue: from normal tissue samples, hyperplasias, low-grade and high-grade dysplasias to gallbladder carcinomas. In all, 115 archived samples of gallbladder tissue from 68 patients, presented after cholecystectomy, were immunohistochemically stained for GLUT-1. According to the intensity of GLUT-1 immunoreactivity, samples were divided into negative (stained 0-10% of cells stained), positive with weak to moderate (10-50%) and positive with strong (>50%) GLUT-1 expression. The GLUT-1 immunoreactivity of the samples showed a characteristic increase from premalignant lesions to carcinomas. Normal gallbladder tissue samples did not express GLUT-1 (100%). Weak expression was shown only focally in hyperplasias, but to a greater extent with low-grade dysplasias (20%), high-grade dysplasias (40%) and carcinomas (51.8%). Normal gallbladder tissue is GLUT-1 negative. GLUT-1 expression in carcinoma tissue is significantly higher than in dysplastic lesions. Strong GLUT-1 expression indicates 100% specificity for detecting gallbladder carcinomas. Therefore, GLUT-1 is a candidate as a diagnostic as well as a tissue prognostic marker in gallbladder carcinoma patients.
Next to age and gender of patients, hypoxia of gallbladder tumours is a factor influencing survival. Among hypoxic factors, GLUT-1 expression is an important (significant) denominator of poor prognosis in gallbladder carcinomas, but not COX-2 nor angiogenesis.
Neo-angiogenesis may have an important role in the poor prognosis of gallbladder carcinoma. An enhanced expression of COX-2 was found in precancerous lesions and in gallbladder carcinoma, likely to be involved in carcinogenesis as well as in angiogenesis. To study the relationships between the COX-2 expression and degree of vascularization, as well as to evaluate their role in the prognosis of patients with gallbladder carcinoma. 27 cases of gallbladder adenocarcinoma were included, classified grading I-III according the WHO classification. The COX-2 and endothelial antigen CD105 expressions were assessed immunohistochemically. COX-2 expression was evaluated according to the percentage and staining intensity of positive cells into "COX-2 positive" and "COX-2 negative" groups. In order to assess tumor microvessel density (MVD), CD105 positively stained microvessels were counted for each specimen in predominantly vascular areas (hot spots) at 200 x magnification. The MVD ranged from 9 to 46 microvessels/field. 15 tumors belonged to the hypervascular group (MVD > or = 25) and 12 to the hypovascular group. There were 16 (59.2%) COX-2 positive cases. There was difference in the degree of angiogenesis between COX-2 positive vs. COX-2 negative group: 11 (68.8%) out of 16 "COX-2 positive" tumors were hypervascular, in comparison with just 4 (36.4%) of "COX-2 negative" tumors. Our data show that the MVD corresponds to the COX-2 overexpression in gallbladder carcinomas. Augmented tumor neovascularization induced by COX-2 might be responsible for the poor prognosis in gallbladder carcinoma patients.
The aims of the study were to investigate the histopathologic characteristics of atherosclerotic lesions and to evaluate the role of apoptosis or programmed cell death in diffuse coronary atherosclerosis. The study included 59 patients who underwent coronary artery bypass grafting coupled with coronary endarterectomy because of diffuse coronary atherosclerosis. Histopathologic analysis of endarterectomy sequesters showed atheroma with confluent extracellular lipid core-type IV lesions in 13 cases (22%); atheroma with lipid core and a cap of fibromuscular layers-type V lesions in 9 cases (15.3%); predominantly calcified fibrous tissue-type VII lesions in 13 cases (22%); and predominantly fibrous tissue-type VIII lesions in 24 cases (40.7%). TUNEL-positive cells were observed in 4 endarterectomy sequesters (6.8%) of subjects with diffuse coronary atherosclerosis. TUNEL-positive cells were demonstrated in the area of mononuclear infiltrates as well as in the vessel wall. The percentage of TUNEL-positive cells in mononuclear infiltrates was 0.5%. Intense mononuclear infiltrates in tunica intima were found in 50% of sequesters, and they consisted of macrophages (40%), T-lymphocytes (17%), and B-lymphocytes (14%). In the area of infiltrates the proportion of MIB-1-positive cells was 2.7%, which was higher than in the intima outside the area of infiltrates (0.5%). In conclusion, apoptosis, which is confined to mononuclear infiltrates, is most likely involved in the development of diffuse coronary atherosclerosis; however, the percentage of apoptotic cells was low (0.5%). A higher proportion of apoptotic cells in the area of infiltrates compared to the rest of the intima was associated with a higher proportion of MIB-1-positive cells. Atherosclerotic lesions in diffuse coronary atherosclerosis were advanced, with a predominance of type VII to VIII lesions.
BACKGROUND AND PURPOSE: To investigate the histopathologic characteristics of atherosclerotic lessions in diffuse coronary artery disease and to evaluate the possible inflammatory role of chronic infection with Chlamydia pneumoniae (CP).MATERIALS AND METHODS: For 10 patients (males, mean age 61 years) who were surgically treated for grave diffuse coronary artery disease, histomorphological analyses of endarterectomized segments of the coronary arteries were performed. Serological analyses for the detection of CP antibodies in peripheral blood were done, preoperatively.RESULTS AND CONCLUSIONS: Diffuse and concentric atherosclerotic changes from VI to VIII stage according to the Stary classification were found. Immunohistochemical methods revealed infiltrates of T-lymphocytes (80% of cases), B-lymphocytes (40% of cases) and macrophages (80%). Using the nuclear marker for proliferation activity MIB-1, single MIB-1 positive cells were found in 40% of cases. Features of arteriologenesis and vasculitis of newly formed arterioles (as well as thickening of the wall of newly formed arterioles) were found in the vessel wall of 8 patients, 7 of them had chronic infection with CP (preoperative micro-immunofluorescent test results: 1:32<IgG ≥1:512 and IgA≥32), one had passed CP infection (1:32 ≤IgG<1:512, IgA negative). These features were absent in 2 patients, both recovered from CP infection and had not the chronic CP infection at the time of surgery. DNA of Chlamydia pneumoniae was detected using the polymerase chain reaction (PCR) method in the vessel wall of 3 patients who were chosen randomly for this method. This study suggests an inflammatory and proatherogenic role of CP in a high grade atherosclerotic coronary artery wall in diffuse coronary artery disease.
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