Polkowski W, van Lanschot J J, Ten Kate F J, Baak J P, Tytgat G N, Obertop H, Voorn W J, Offerhaus G J
Department of Surgery, University of Amsterdam, The Netherlands.
Surg Oncol. 1995 Jun;4(3):163-71. doi: 10.1016/s0960-7404(10)80021-0.
In the Barrett's oesophagus (BE) progression from metaplasia, via dysplasia, into invasive cancer, an aberrant cell proliferation governed by genetic change plays a central role. Alterations of the p53 tumour-suppressor gene appear especially critical and, like the proliferation marker Ki67, can be detected by immunohistochemistry. The purpose of this study therefore was to investigate the clinical value of p53 and Ki67 as markers for tumour progression in BE, and at the same time test the validity of the concept of a metaplasia-dysplasia-carcinoma sequence in BE by correlating the expression of these markers with various grades of dysplasia. Thirty-two lesions (seven negative for dysplasia, five indefinite for dysplasia, 11 low-grade dysplasia and nine high-grade dysplasia) from 25 archival resection specimens were selected for study. Increasing grades of dysplasia showed increasingly p53 accumulation; p53 accumulation was never observed in mucosa without dysplasia. The increasing p53 expression was accompanied by an increased Ki67-labelling index and an upward shift of the proliferative compartment. The results lend support to the multistep progression model of a metaplasia-dysplasia-carcinoma sequence in BE. Expression of p53 and Ki67, markers which can be easily applied on archival material, can be valuable adjuncts for the histopathological diagnosis of dysplasia and may have predictive value for cancer risk.
在巴雷特食管（BE）从化生经发育异常进展为浸润性癌的过程中，由基因改变控制的异常细胞增殖起着核心作用。p53肿瘤抑制基因的改变似乎尤为关键，并且与增殖标志物Ki67一样，可通过免疫组织化学检测到。因此，本研究的目的是探讨p53和Ki67作为BE肿瘤进展标志物的临床价值，同时通过将这些标志物的表达与不同程度的发育异常相关联，来检验BE中化生-发育异常-癌序列概念的有效性。从25份存档切除标本中选取32个病变（7个发育异常阴性、5个发育异常不确定、11个低级别发育异常和9个高级别发育异常）进行研究。发育异常程度增加显示p53积累增加；在无发育异常的黏膜中从未观察到p53积累。p53表达增加伴随着Ki67标记指数增加以及增殖区的上移。结果支持了BE中化生-发育异常-癌序列的多步骤进展模型。p53和Ki67的表达可轻松应用于存档材料，是发育异常组织病理学诊断的有价值辅助手段，并且可能对癌症风险具有预测价值。
