In healthy volunteers, immunohistochemistry supports squamous to columnar metaplasia as mechanism of expansion of cardia, aggravated by central obesity
In healthy volunteers, immunohistochemistry supports squamous to columnar metaplasia as mechanism of expansion of cardia, aggravated by central obesity
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DOI：
10.1136/gutjnl-2014-308914
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发表时间：
2015-11-01
期刊：
影响因子：
24.5
通讯作者：
McColl, Kenneth E. L.
中科院分区：
文献类型：
--
作者：
Derakhshan, Mohammad H.;Robertson, Elaine V.;McColl, Kenneth E. L.
前言：最近，我们发现健康志愿者的心脏粘膜长度与年龄和肥胖有关。我们现在已经检查了这个扩张的贲门的免疫组织学特征，以确定它是否可能是由于远端食道的柱状化生。方法我们使用了鳞状结肠交界处(SCJ)、胃窦和体部活组织检查，这些标本来自52名幽门螺杆菌阴性的健康志愿者，他们在早期的生理研究中没有食道裂孔疝、跨括约肌反流、Barrett‘s食道或肠上皮化生(IM)。在SCJ、胃窦和体部的鳞状、心脏和氧合-心脏粘膜，对炎症细胞密度和反应性异型性进行评分。切片进行尾型同源异型盒2(CDX-2)、绒毛蛋白、三叶因子家族3(TFF-3)和肝肠(LI)-钙粘蛋白、粘蛋白MUC1、MUC-2和MUC-5AC染色。此外，对15例患有/不患有IM的Barrett病患者的活检组织进行了染色和评分作为比较。免疫组织学特征与肥胖参数和高分辨pH值记录相关。结果心脏粘膜的炎性浸润强度与非IM Barrett相似，但高于其他任何上消化道粘膜。心脏粘膜的免疫染色模式与非IM Barrett‘s最为相似，只是CDX-2免疫染色稍弱。在远端食道鳞状上皮中，柱状分化标志物TFF3和LI-钙粘附素的表达明显，并与中心性肥胖相关(相关系数分别为0.604和0.462，P=0.002)。此外，Tff-3在食道远端鳞状上皮中的表达与食道下括约肌胃酸度近端延伸呈正相关(CC=-0.538，p=0.001)。结论这些结果与健康志愿者食道远端鳞状上皮化生所致的贲门扩张相一致，并随中心性肥胖的加重而加重。幽门螺杆菌或跨括约肌酸反流导致的贲门腺癌有很大比例不是由幽门螺杆菌或跨括约肌酸反流引起的。
Introduction Recently, we showed that the length of cardiac mucosa in healthy volunteers correlated with age and obesity. We have now examined the immunohistological characteristics of this expanded cardia to determine whether it may be due to columnar metaplasia of the distal oesophagus.Methods We used the squamocolumnar junction (SCJ), antral and body biopsies from the 52 Helicobacter pylori-negative healthy volunteers who had participated in our earlier physiological study and did not have hiatus hernia, transsphincteric acid reflux, Barrett's oesophagus or intestinal metaplasia (IM) at cardia. The densities of inflammatory cells and reactive atypia were scored at squamous, cardiac and oxyntocardiac mucosa of SCJ, antrum and body. Slides were stained for caudal type homeobox 2 (CDX-2), villin, trefoil factor family 3 (TFF-3) and liver-intestine (LI)-cadherin, mucin MUC1, Muc-2 and Muc-5ac. In addition, biopsies from 15 Barrett's patients with/without IM were stained and scored as comparison. Immunohistological characteristics were correlated with parameters of obesity and high-resolution pH metry recording.Results Cardiac mucosa had a similar intensity of inflammatory infiltrate to non-IM Barrett's and greater than any of the other upper GI mucosae. The immunostaining pattern of cardiac mucosa most closely resembled non-IM Barrett's showing only slightly weaker CDX-2 immunostaining. In distal oesophageal squamous mucosa, expression of markers of columnar differentiation (TFF-3 and LI-cadherin) was apparent and these correlated with central obesity (correlation coefficient (CC)=0.604, p=0.001 and CC=0.462, p=0.002, respectively). In addition, expression of TFF-3 in distal oesophageal squamous mucosa correlated with proximal extension of gastric acidity within the region of the lower oesophageal sphincter (CC=-0.538, p=0.001).Conclusions These findings are consistent with expansion of cardia in healthy volunteers occurring by squamo columnar metaplasia of distal oesophagus and aggravated by central obesity. This metaplastic origin of expanded cardia may be relevant to the substantial proportion of cardia adenocarcinomas unattributable to H. pylori or transsphincteric acid reflux.