Shamma A, Yamamoto H, Doki Y, Okami J, Kondo M, Fujiwara Y, Yano M, Inoue M, Matsuura N, Shiozaki H, Monden M
Department of Surgery II, Osaka University Medical School, Suita City, Japan.
Clin Cancer Res. 2000 Apr;6(4):1229-38.
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.
环氧化酶-2（COX-2）在包括食管鳞状细胞癌（SCC）在内的多种人类恶性肿瘤中过表达，但关于COX-2在癌前食管鳞状发育异常中的表达情况知之甚少。为了阐明COX-2在食管癌发生中的作用，我们检测了该酶在正常鳞状上皮（n = 42）、鳞状发育异常[高级别发育异常（HGD，n = 41；低级别发育异常（LGD，n = 33）]、原位癌（n = 16）、黏膜浸润癌（n = 18）和晚期SCC（n = 45）中的表达。免疫组化显示，与其他病变相比，HGD中COX-2表达显著升高。COX-2评分是由COX-2染色强度和阳性率确定的指标（最高3.0），在正常食管中为0.29±0.04，LGD中为1.75±0.11，HGD中为2.89±0.05，原位癌中为2.17±0.18，黏膜浸润癌中为1.95±0.22，晚期SCC中为1.81±0.08。逆转录-聚合酶链反应检测结果证实了免疫组化结果。在发育异常病变中，COX-2表达与通过增殖细胞核抗原指数评估的增殖活性相关（P = 0.001），但在SCC中不相关。SCC中COX-2表达与包括预后在内的各种临床病理参数均无相关性。我们的结果表明，COX-2是HGD的敏感标志物，并提示COX-2可能参与食管鳞状细胞癌发生的早期阶段。
