Cyclooxygenase-2 Expression and Relationship to Malignant Potential in Human Bladder Cancer.

Ichiro Matsuzawa,Go Kimura,Yukihiro Kondo,Masao Akimoto,Shuntaro Hara,Yoshitaka Hashimoto,Shigeo Horie,Nobumasa Imura

doi:10.1248/jhs.48.42

Ichiro Matsuzawa, Go Kimura + Show 6 more

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https://doi.org/10.1248/jhs.48.42

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Journal: Eisei kagaku	Publication Date: Jan 1, 2002
Citations: 5	License type: cc-by

Affiliation: Nippon Medical School, The University of Tokyo

Abstract

Cyclooxygenase (COX), which catalyzes the synthesis of prostaglandins from arachidonic acid, has two isoforms; COX-1 and COX-2. A large body of evidence exists to suggest that COX-2 is important in gastrointestinal cancer. In order to determine whether COX-2 is expressed in transitional cell carcinoma (TCC) of the human bladder as well as in gastrointestinal cancer, we investigated COX-2 expression in human TCC by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and immunohistochemical analysis, and we found that normal bladder epithelium did not express COX-2 and that COX-2 was markedly up-regulated in human bladder TCC. In nontumor tissues, COX-2 immunostaining signals were observed only in lymphoid follicles. Furthermore, the intensity and extent of COX-2 immunostaining in the bladder cancer tissues were scored and the relationship to tumor grade and stage was investigated. The levels of COX-2 expression were correlated with the tumor grade; from grades 1 to 3, there was a stepwise increase in the COX-2 immunostaining score. These findings suggested that an increase in COX-2 expression may be associated with bladder carcinogenesis as well as gastrointestinal carcinogenesis, and that it may be useful as a biomarker in bladder cancer.

Highlights

Bladder cancer is the most common malignancy of the urinary tract, and the fourth or fifth leading cause of cancer-related death of men in Western industrialized countries.1) The prognosis of patients with advanced bladder cancer is still extremely poor despite recent therapeutic advances, such as improved surgical techniques and perioperative combination chemotherapy
The COX-2 gene is an immediate early-response gene that is induced by growth factors, oncogenes, carcinogens, and tumor-promoting phorbol esters.5) Multiple lines of evidence suggest that COX-2 is important in carcinogenesis, and COX-2 is up-regulated in transformed cells6) and in various forms of gastrointestinal cancer,7–10) whereas levels of COX-1 are relatively constant
We further showed that from grades 1 to grade 3, there was a stepwise increase in the COX2 score

Summary

Introduction

Bladder cancer is the most common malignancy of the urinary tract, and the fourth or fifth leading cause of cancer-related death of men in Western industrialized countries.1) The prognosis of patients with advanced bladder cancer is still extremely poor despite recent therapeutic advances, such as improved surgical techniques and perioperative combination chemotherapy. Future improvement in the survival rate of patients with bladder cancer might be possible through the development of novel indicator or therapeutic strategies. The COX-2 gene is an immediate early-response gene that is induced by growth factors, oncogenes, carcinogens, and tumor-promoting phorbol esters.5) Multiple lines of evidence suggest that COX-2 is important in carcinogenesis, and COX-2 is up-regulated in transformed cells6) and in various forms of gastrointestinal cancer,7–10) whereas levels of COX-1 are relatively constant. A null mutation for COX-2 resulted in a marked reduction in the number and size of intestinal polyps in APC mice, a murine model of familial adenomatous polyposis.11) In addition to the genetic evidence implicating COX-2 in tumorigenesis, newly developed selective inhibitors of COX-2 protect against gastrointestinal tumor formation.12)

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