Pavlov Kirill, Honing Judith, Meijer Coby, Boersma-van Ek Wytske, Peters Frans T M, van den Berg Anke, Karrenbeld Arend, Plukker John T M, Kruyt Frank A E, Kleibeuker Jan H
Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Surgical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Dig Liver Dis. 2015 Jan;47(1):73-80. doi: 10.1016/j.dld.2014.09.014. Epub 2014 Oct 16.
Barrett's oesophagus can progress towards oesophageal adenocarcinoma through a metaplasia-dysplasia-carcinoma sequence, but the underlying mechanisms are poorly understood. The transcription factor GATA6 is known to be involved in columnar differentiation and proliferation, and GATA6 gene amplification was recently linked with poor survival in oesophageal adenocarcinoma.
To study the expression of GATA6 during Barrett's oesophagus development and malignant transformation. To determine the prognostic value of GATA6 in oesophageal adenocarcinoma.
Two retrospective cohorts were derived from the pathological archive of the University Medical Center Groningen. The first cohort contained 130 tissue samples of normal squamous epithelium, metaplasia, dysplasia and oesophageal adenocarcinoma. The second cohort consisted of a tissue microarray containing tissue from 92 oesophageal adenocarcinoma patients. Immunohistochemistry was used to examine GATA6 protein expression and to correlate GATA6 expression in oesophageal adenocarcinoma with overall and disease-free survival.
The percentage of GATA6-positive cells was low in squamous epithelium (10%) but increased progressively in Barrett's oesophagus (30%, P < 0.001) and high-grade dysplasia (82%, P = 0.005). GATA6 expression was not associated with overall or disease-free survival in oesophageal adenocarcinoma patients (P = 0.599 and P = 0.700 respectively).
GATA6 expression is progressively increased during Barrett's oesophagus development and its malignant transformation. However, no prognostic value of GATA6 expression could be found in oesophageal adenocarcinoma.
巴雷特食管可通过化生-发育异常-癌序列发展为食管腺癌,但其潜在机制尚不清楚。已知转录因子GATA6参与柱状上皮分化和增殖,最近GATA6基因扩增与食管腺癌患者的不良预后相关。
研究GATA6在巴雷特食管发育和恶性转化过程中的表达。确定GATA6在食管腺癌中的预后价值。
两个回顾性队列来自格罗宁根大学医学中心的病理档案。第一个队列包含130份正常鳞状上皮、化生、发育异常和食管腺癌的组织样本。第二个队列由一个组织芯片组成,包含92例食管腺癌患者的组织。采用免疫组织化学法检测GATA6蛋白表达,并将食管腺癌中GATA6表达与总生存期和无病生存期进行关联分析。
GATA6阳性细胞百分比在鳞状上皮中较低(10%),但在巴雷特食管中逐渐增加(30%,P<0.001),在高级别发育异常中较高(82%,P=0.005)。GATA6表达与食管腺癌患者的总生存期或无病生存期均无关(分别为P=0.599和P=0.700)。
在巴雷特食管发育及其恶性转化过程中,GATA6表达逐渐增加。然而,在食管腺癌中未发现GATA6表达具有预后价值。