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.

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