Cobbe Sarah C, Scobie Gillian C, Pohler Elizabeth, Hayes John D, Kernohan Neil M, Dillon John F
Department of Molecular and Cellular Pathology, Biomedical Research Centre, University of Dundee, UK.
Eur J Gastroenterol Hepatol. 2003 Jan;15(1):41-7. doi: 10.1097/00042737-200301000-00008.
Oesophageal cancer associated with the premalignant condition Barrett's oesophagus has increased in incidence over the last few years. Phase II detoxifying enzymes, including glutathione S-transferases (GSTs) protect the mucosa from carcinogens, which can cause oxidative damage to cells. Therefore, a reduction in these anti-oxidant enzymes can increase the risk of carcinogenesis. The aim of this study was to compare the extent of GST expression in normal oesophageal tissue, Barrett's oesophagus and oesophageal adenocarcinoma.
Antibodies raised against GST alpha, GST mu, GST pi and microsomal GST were used to identify expression of these proteins in tissue sections.
Paraffin-embedded sections were stained using standard immunohistochemical techniques to demonstrate the pattern of expression of GST proteins in biopsy specimens. Twelve sections of Barrett's metaplasia and an equal number of specimens from normal oesophageal tissue were examined, together with sections from adenocarcinoma and normal gastric mucosa.
Expression of the GST enzymes appeared to be reduced in Barrett's tissue compared to normal oesophageal tissue. Nuclear staining featured in some of the normal tissue sections, but not in Barrett's tissue.
The reduction in GST expression suggested in Barrett's tissue is an interesting finding, as it is possible that reduced expression of these detoxifying enzymes may contribute to the risk of development of adenocarcinoma in Barrett's mucosa.
在过去几年中,与癌前病变巴雷特食管相关的食管癌发病率有所上升。包括谷胱甘肽S-转移酶(GSTs)在内的II期解毒酶可保护黏膜免受致癌物侵害,致癌物会对细胞造成氧化损伤。因此,这些抗氧化酶水平的降低会增加致癌风险。本研究的目的是比较正常食管组织、巴雷特食管和食管腺癌中GST表达的程度。
使用针对GSTα、GSTμ、GSTπ和微粒体GST产生的抗体来鉴定这些蛋白质在组织切片中的表达。
采用标准免疫组织化学技术对石蜡包埋切片进行染色,以显示活检标本中GST蛋白的表达模式。检查了12个巴雷特化生切片以及相同数量的正常食管组织标本,同时检查了腺癌和正常胃黏膜的切片。
与正常食管组织相比,巴雷特组织中GST酶的表达似乎有所降低。一些正常组织切片有核染色,但巴雷特组织中没有。
巴雷特组织中GST表达降低是一个有趣的发现,因为这些解毒酶表达降低可能会增加巴雷特黏膜发生腺癌的风险。