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

Motoi Kondo, Hirofumi Yamamoto, Hiroaki Nagano, Jiro Okami, Yasuhiro Ito, Junzo Shimizu, Hidetoshi Eguchi, Atsushi Miyamoto, Keizo Dono, Koji Umeshita, Nariaki Matsuura, Ken Ichi Wakasa, Shoji Nakamori, Masato Sakon, Morito Monden

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Abstract

Recent studies have shown increased levels of cyclooxygenase-2 (COX-2) in a variety of human malignancies including hepatocellular carcinoma (HCC), but little is known about the prognostic value of COX-2 in HCC or its associated nontumor liver tissue. We examined the expression of COX-2 protein by immunohistochemistry in 53 patients with HCCs whose corresponding nontumor tissues were hepatitis C virus-related chronic hepatitis (n = 21) and cirrhosis (n = 32). Samples of nine histologically normal livers and eight precancerous dysplasias were also analyzed. The level of COX-2 increased from normal liver to chronic hepatitis to cirrhosis. The majority of cirrhotic livers (81%) displayed marked COX-2 expression. In dysplasias, COX-2 expression was mainly moderate or strong (88%). In HCC, 17% of samples displayed a high COX-2 expression, and 37% of samples expressed COX-2 at a moderate level. Concordant results were obtained with reverse transcription- PCR and Western blot analyses. Clinicopathological survey indicated a significant correlation between COX-2 expression and differentiated carcinoma (P = 0.019). Although there was no correlation between COX-2 expression in HCC and prognosis, a striking difference was found between COX-2 expression in nontumor tissue and shorter disease-free survival (P = 0.0132). Moreover, high COX-2 expression 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 HCC after surgery.

Original languageEnglish
Pages (from-to)4005-4012
Number of pages8
JournalClinical Cancer Research
Volume5
Issue number12
Publication statusPublished - Dec 1999

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Kondo, M., Yamamoto, H., Nagano, H., Okami, J., Ito, Y., Shimizu, J., Eguchi, H., Miyamoto, A., Dono, K., Umeshita, K., Matsuura, N., Wakasa, K. I., Nakamori, S., Sakon, M., & Monden, M. (1999). Increased expression of COX-2 in nontumor liver tissue is associated with shorter disease-free survival in patients with hepatocellular carcinoma. Clinical Cancer Research, 5(12), 4005-4012.