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Angiogenesis correlates with cycloogygenase-2<br />
(COX-2) expression as well as with the tumour grade<br />
in gallbladder carcinoma<br />
Mateja Legan 1 , Bo{tjan Luzar 2 , Vera Ferlan Marolt 2 , Andrej Cör 1<br />
1<br />
Institute of Histology & Embryology, 2 Institute of Pathology, Medical Faculty<br />
University of Ljubljana, Korytkova 2 , 1000 Ljubljana, Slovenia<br />
Introduction and aim: Carcinoma of the gallbladder is an agressive tumor with an overall<br />
5-year survival rate of less than 5%. Activation of the angiogenic pathways is common<br />
and, by inducing new blood vessel formation, may have a decisive role in determining<br />
local invasion, matestasis and clinical outcome. The proliferative endothelial antigen<br />
CD105 (endoglin) essencial for angiogenesis and vascular development serves as a<br />
marker of tumour neovasculature. Enhanced expression of cyclooxygenase-2 (COX-2)<br />
was found in precancerous lessions and in gallbladder carcinoma, which is likely to<br />
be involved in carcinogenesis as well as in angiogenesis.<br />
The aim of the study was to investigate the relationships between the expression of<br />
COX-2 and degree of vascularization, clinicopathological features and survival time of<br />
patients with gallbladder carcinoma.<br />
Materials and Methods: A retrospective analysis was performed on 27 gallbladder<br />
adenocarcinoma tissue specimens obtained from patients operatively treated (11 male<br />
and 16 female patients, mean age 66.5 +/- 11.0 years). Gallbladder adenocarcinomas<br />
were classified according to the WHO classification of gallbladder tumours: 8 were<br />
well-differentiated, 4 moderately and 15 poorly-differentiated.<br />
The expression of COX-2 and CD105 was assessed by immunohistochemical method.<br />
COX-2 expression was evaluated according to the percentage of positive cells and the<br />
intensity of staining. Regarding immuno-reactive score gallbladder carcinomas were<br />
divided into »COX-2 positive« and »COX-2 negative« groups. For microvessel count<br />
(MVC) assessment the areas containing a large number of microvessels were identified.<br />
Image analysis system LUCIA G (Nikon, Japan) was used for MVC quantification. The<br />
average number of microvessels in 10 light microscopic field at 200x magnification was<br />
recorded as the MVC for each tumour. Tumours were separated into hypervascular<br />
and hypovascular group.<br />
Results and conclusions: The MVC ranged from 9 to 46 (mean 25.6 +/- 9.2).15<br />
tumours belonged to hypervascular group (mean microvessel count >= 25) and 12 to<br />
hypovascular group (MVC