Cheong E, Igali L, Harvey I, Mole M, Lund E, Johnson I T, Rhodes M
General Surgery Department, Norfolk and Norwich University Hospital, Colney, UK.
Aliment Pharmacol Ther. 2003 Feb;17(3):379-86. doi: 10.1046/j.1365-2036.2003.01432.x.
The incidence of Barrett's oesophageal adenocarcinoma is increasing more rapidly than any other malignancy in industrialized countries. Cyclo-oxygenase-2 appears to play an important role in gastrointestinal carcinogenesis. Previous studies on cyclo-oxygenase-2 expression in Barrett's oesophageal carcinogenesis have utilized tissue samples obtained from different patients. We sought a definitive comparison of cyclo-oxygenase-2 expression in the sequence of Barrett's metaplasia-dysplasia-adenocarcinoma within the same patients.
Paraffin-embedded oesophago-gastrectomy specimens from 20 patients, containing successive stages of Barrett's metaplasia, high-grade dysplasia and adenocarcinoma, were analysed for cyclo-oxygenase-2 expression by immunohistochemistry.
Cyclo-oxygenase-2 was constitutively expressed in the basal layers of cells in the adjacent normal squamous oesophageal epithelium, but a higher cyclo-oxygenase-2 expression was observed in Barrett's metaplasia. A further increase in cyclo-oxygenase-2 expression was detected in high-grade dysplasia, but cyclo-oxygenase-2 was decreased in adenocarcinoma tissue, regardless of its stage or level of differentiation.
Cyclo-oxygenase-2 expression is progressively increased when squamous oesophageal epithelium develops into Barrett's metaplastic epithelium and then into high-grade dysplasia, but appears to decrease when adenocarcinoma develops. These findings may be significant for an effective chemo-prevention strategy with selective cyclo-oxygenase-2 inhibitors.
在工业化国家,巴雷特食管腺癌的发病率增长速度比其他任何恶性肿瘤都要快。环氧化酶-2似乎在胃肠道致癌过程中发挥重要作用。以往关于环氧化酶-2在巴雷特食管致癌过程中表达的研究使用的是从不同患者获取的组织样本。我们试图对同一患者巴雷特化生-发育异常-腺癌序列中环氧化酶-2的表达进行明确比较。
对20例患者的石蜡包埋食管胃切除术标本进行免疫组织化学分析,这些标本包含巴雷特化生、高级别发育异常和腺癌的连续阶段。
环氧化酶-2在相邻正常鳞状食管上皮细胞的基底层中组成性表达,但在巴雷特化生中观察到更高的环氧化酶-2表达。在高级别发育异常中检测到环氧化酶-2表达进一步增加,但在腺癌组织中环氧化酶-2表达降低,无论其分期或分化程度如何。
当鳞状食管上皮发展为巴雷特化生上皮然后发展为高级别发育异常时,环氧化酶-2表达逐渐增加,但在腺癌发生时似乎降低。这些发现对于使用选择性环氧化酶-2抑制剂的有效化学预防策略可能具有重要意义。