763
Cyclooxygenase-2 in Dukes B Colon Cancer
Background/Aims: To demonstrate immunohis-
tochemical expression of COX-2 protein in Dukes
B colon cancer and to establish a correlation with
clinicopathological parameters such as: age, gen-
der, gradus, presence of vascular invasion and pa-
tient’s overall survival.
Methodology: We performed immunohistochem-
ical analysis of formalin-ixed, parafin embedded
specimens form 152 Dukes B colon carcinomas,
using the COX-2 monoclonal antibody. Immuno-
histochemical results were scored semi-quanti-
tatively. Carcinomas were graded as low or high
grade. Survival time was analyzed by Kaplan-
Meier method, and the log-rank test was used to
assess the differences between groups. For multi-
variate analysis, Cox proportional hazard regres-
sion model was used to examine several param-
eters simultaneously.
Results: Univariate analysis showed that posi-
tive staining for COX-2, high histological grade;
vascular invasion; male gender and age over
60 years, were connected with shorter survival
of patients with Dukes B colon cancer (0.023<
p<0.001). However, multivariate analysis have
shown that the high COX-2 expression in Duke’s
B colon cancer was unrelated to overall patient
survival (RR=1.4; p=0.311).
Conclusion: Expression of COX-2 in tumor epi-
thelial cells does not seem to be related to survival
in patients with colon cancer Dukes B.
ABSTRACT
INTRODUCTION
Colorectal cancer, one of the most prevalent
cancers worldwide, is the third leading cause of
cancer related mortality in developed countries (1).
Despite improvements in surgical and adjuvant
chemotherapy treatment, mortality from colorectal
carcinoma (CRC) remains high in Western coun-
tries, with metastatic spread to the liver in approxi-
mately 50% of patients (2).
Although staging remains the most widely used
prognostic indicator for CRC, there is increasing
evidence that it is insuficient to predict the clinical
outcome of patients with CRC, particularly those
with intermediate stage diseases (Dukes B, T3, T4,
N0, M0), for which clinical management has yet to
be standardized.
Biological prognostic markers underlying invasion
and metastasis may help improve clinical staging and
provide useful information for the application of vari-
ous novel therapeutic strategies aimed at controlling
disease progression and tumor cell dissemination (2).
In recent years, the role of a key enzyme in
prostaglandin synthesis, cyclooxygenase (COX-2),
has been appreciated in cancer development and
progression. COX-2 is responsible for the conver-
sion of arachidonic acid to prostaglandins and other
eicosanoids. In addition to its well-known role in in-
lammatory reactions, COX-2 plays a role in tumor
progression, angiogenesis, metastasis and abroga-
tion of the antitumor immune response (3-6). COX-
2 prevents apoptosis by generation of antiapoptotic
PGE2 (7) and PGI2 (8), and by removal of the proa-
poptotic substrate arachidonic acid (9). PGE2 in-
duces transformations that result in increased Bcl-
2 expression and prolong the cell cycle G1 phase
with increased cyclin D1 expression (10). Numer-
ous epidemiological studies have indicated that the
use of non-steroidal anti-inlammatory drugs, and
Željko Šundov
1
, Nenad Kunac
2
, Vesna Čapkun
3
, Marija Kalebić
4
, Nikica Družijanić
5
,
Livia Puljak
6
and Snježana Tomić
2
1
Departments of Internal Medicine,
2
Pathology,
3
Nuclear Medicine,
5
Surgery and
6
Histology and
Embryology, School of Medicine, University of Split, Croatia.
4
Department of Emergency Medicine, County of Split-Dalmatia, Croatia.
Corresponding author: Nenad Kunac, Department of Pathology, School of Medicine,
University of Split, Spinčićeva 1, 21000 Split, Croatia
Tel.: +38521556486, Fax: +38521389510, E-mail: nenadkunac@gmail.com
KEY WORDS:
COX-2; Colon
cancer; Immu-
nohistochemistry;
Prognosis
FIGURE 1 Cumu-
lative survival in
relation to COX-2
expression.
COX-2 expression
Positive ---
Negative - -
Hepato-Gastroenterology 2011; 58:763-768
© H.G.E. Update Medical Publishing S.A., Athens-Stuttgart