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Clinical Cancer Research Vol. 6, 1229-1238, April 2000
© 2000 American Association for Cancer Research

Advances in Brief

Up-Regulation of Cyclooxygenase-2 in Squamous Carcinogenesis of the Esophagus1

Awad Shamma2, Hirofumi Yamamoto, Yuichiro Doki, Jiro Okami, Motoi Kondo, Yoshiyuki Fujiwara, Masahiko Yano, Masatoshi Inoue, Nariaki Matsuura, Hitoshi Shiozaki and Morito Monden

Department of Surgery II, Osaka University Medical School [A. S., H. Y., Y. D., J. O., M. K., Y. F., M. Y., M. I., H. S., M. M.], and Department of Pathology, School of Allied Health Science, Faculty of Medicine, Osaka University [N. M.], Osaka 565-0871, Japan

Cyclooxygenase-2 (COX-2) is overexpressed in various types of human malignancies including squamous cell carcinomas (SCCs) of the esophagus, but little is known about COX-2 expression in premalignant esophageal squamous dysplasia. To elucidate the role of COX-2 in esophageal carcinogenesis, we examined the expression of this enzyme in normal squamous epithelium (n = 42), squamous dysplasia [high-grade dysplasia (HGD, n = 41; low-grade dysplasia (LGD, n = 33)]; carcinoma in situ (n = 16), mucosal invasive carcinoma (n = 18), and advanced SCC (n = 45). Immunohistochemistry showed a significantly high COX-2 expression in HGD compared with other lesions. The COX-2 score, an index determined by intensity and positivity of COX-2 staining (maximum 3.0), was 0.29 ± 0.04 in normal esophagus, 1.75 ± 0.11 in LGD, 2.89 ± 0.05 in HGD, 2.17 ± 0.18 in CIS, 1.95 ± 0.22 in mucosal invasive carcinoma, and 1.81 ± 0.08 in advanced SCC. Results of reverse transcription-PCR assays confirmed those obtained by immunohistochemistry. COX-2 expression correlated with proliferation activity assessed by the proliferating cell nuclear antigen index in dysplastic lesions (P = 0.001) but not in SCCs. COX-2 expression in SCC did not correlate with various clinicopathological parameters including prognosis. Our results indicate that COX-2 is a sensitive marker for HGD and suggest that COX-2 may be involved in early stages of squamous carcinogenesis of the esophagus.




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