Increased expression of COX-2 in nontumor liver tissue is associated with shorter disease-free survival in patients with hepatocellular carcinoma

Recent studies have shown increased levels of cyclooxygenase-2 (COX-2) in a variety of human malignancies including hepatocellular carcinoma (HCC), bu t little is known about the prognostic value of COX-2 in HCC or its associa ted nontumor liver tissue. We examined the expression of COX-2 protein by i mmunohistochemistry in 53 patients with HCCs whose corresponding nontumor t issues were hepatitis C virus-related chronic hepatitis (n = 21) and cirrho sis (n = 32), Samples of nine histologically normal livers and eight precan cerous dysplasias were also analyzed. The level of COX-2 increased from nor mal liver to chronic hepatitis to cirrhosis, The majority of cirrhotic live rs (81%) displayed marked COX-2 expression. In dysplasias, COX-2 expression was mainly moderate or strong (88%), In HCC, 17% of samples displayed a hi gh COX-2 expression, and 37% of samples expressed COX-2 at a moderate level . Concordant results were obtained with reverse transcription-PCR and Weste rn blot analyses. Clinicopathological survey indicated a significant correl ation between COX-2 expression and differentiated carcinoma (P = 0.019), Al though there was no correlation between COX-2 expression in HCC and prognos is, a striking difference was found between COX-2 expression in nontumor ti ssue and shorter disease-free survival (P = 0.0132), Moreover, high COX-2 e xpression in nontumor tissue was significantly correlated with the presence of active inflammation (P < 0.0001), The present findings suggest that COX -2 expression in nontumor tissue may play a positive role in relapse of BCC after surgery.