Expression of cyclooxygenase-2 is associated with p53 accumulation in premalignant and malignant gallbladder lesions.
OBJECTIVE
To examine the relationship between cyclooxygenase-2 (COX-2) overexpression and p53 accumulation in gallbladder carcinoma and its precursor lesions.


METHODS
Sixty-eight gallbladder tissue samples comprising 14 cases of normal gallblader epithelium, 27 cases of dysplasia (11 low-grade dyplasia and 16 high-grade dysplasia) and 27 adenocarcinomas were evaluated by immunohistochemistry for COX-2 expression and p53 accumulation. The relationship among COX-2 expression, p53 accumulation and clinicopathological characteristics was analysed.


RESULTS
COX-2 was expressed in 14.3% of normal gallbladder epithelium, 70.3% of dysplastic epite hlium, and 59.2% of adenocarcinomas. When divided into low- and high-grade dysplasia, COX-2 was positive in 5 (45.4%) cases of low-grade and 14 (87.5%) of high-grade dysplasia (P = 0.019). Accumulation of p53 was detected in 5 (31.2%) cases of high-grade dysplasia and in 13 (48.1%) of carcinomas. No p53 accumulation was found in normal epithelium or low-grade dysplasia. COX-2 overexpression was observed in 17 of 18 (94.4%) cases with p53-accumulation in comparison with 20 (40.0%) out of 50 cases without p53 accumulation (P < 0.001).


CONCLUSIONS
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.
Legan
Mateja
M
Institute for Histology and Embryology, Medical Faculty University of Ljubljana, Slovenia.
Luzar
Bostjan
B
Marolt
Vera Ferlan
VF
Cor
Andrej
A
D000230:Adenocarcinoma / Q000201:enzymology* / Q000503:physiopathology*; D051546:Cyclooxygenase 2 / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D004848:Epithelium / Q000737:chemistry / Q000473:pathology; D005706:Gallbladder Neoplasms / Q000201:enzymology* / Q000503:physiopathology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D011230:Precancerous Conditions / Q000201:enzymology* / Q000503:physiopathology*; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53; D051546:Cyclooxygenase 2