Adenocarcinoma of the oesophagus: is it gastric cancer?
Adenocarcinoma of the oesophagus: is it gastric cancer?
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DOI：
10.1136/gutjnl-2022-327096
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发表时间：
2023-06
期刊：
影响因子：
24.5
通讯作者：
Bass, Adam J.
中科院分区：
文献类型：
--
作者：
Quante, Michael;Wang, Timothy C.;Bass, Adam J.
胃-食管交界处（GEJ）癌，包括食管癌（EAC）和结合部胃腺癌，在西方国家的发病率急剧增加，与非贲门胃癌（GC）的减少相关。更好地了解这些癌症的起源和发病机制可能有助于改进癌症的预防、检测和治疗。GEJ腺癌包括过去被分类为食道或胃起源的肿瘤。多年来，位于GEJ上方的腺癌（即EAC）被视为与GC不同的实体。这种观点与EAC与巴雷特食管（BE）密切相关，巴雷特食管是下食管的一种化生状态，被认为是胃酸反流时正常鳞状上皮向肠化粘膜的转分化。这种EAC起源于鳞状的假设导致：(1)对BE患者进行了广泛的监测，(2)在一些临床试验中将食管鳞状（ESCC）和腺癌（EAC）纳入其中，(3)将EAC与GC明确区分开来。我们在此提出基于对GEJ癌起源和发病机制的新见解来重新思考这种方法。近年来，通过对人类样本的深入分析以及来自人类细胞和小鼠模型的实验结果，出现了支持胃源性EAC/BE的新数据。2012年，基于对BE （L2-IL-1b）小鼠模型的谱系追踪研究结果，提出了BE起源于贲门的假设，该模型概括了从食管炎到不典型增生的组织学进展。谱系追踪允许干细胞及其后代的遗传定义和跟踪，并有助于确定肿瘤的细胞起源。随后，癌症基因组图谱研究网络（TCGA）于2017年对食管癌和胃癌进行了全面的分子基因组分析，证实了食管癌EAC和ESCC两种组织学亚型的明显特征，其中ESCC与头颈部SCC的相似性更大。此外，EAC和GC的联合分析不能识别出明确区分EAC与染色体不稳定性（CIN）类GC的特征，表明它们有共同的起源。相比之下，在胃非贲门区域更常见的胃癌变异，包括伴有微卫星不稳定的肿瘤、Epstein-Barr病毒感染或弥漫性组织学类型，在贲门和EAC的胃癌中不太常见。TCGA的遗传结果与最近对BE与正常胃和食管组织的表观遗传学研究一致，这些研究也证明了BE起源于胃的证据。此外，最近的一项研究利用全面的单细胞转录组学分析、计算机谱系追踪、从近端胃到鳞状食管健康和患病供体的人类组织的突变分析，表明BE通过不同的转录程序起源于贲门祖细胞。后一项研究还通过实验确定了人胃组织类器官培养物分化为BE的能力。事实上，这种新兴的BE/EAC起源于胃组织的观点与关键的病理发现是一致的，BE总是开始于非常远的食道，与贲门相连，并且BE包括胃和肠细胞类型的嵌合，这在很大程度上与胃中的肠化生难以区分。这种关于EAC关系的新思考与……的原始描述相呼应。
The incidence of gastro-oesophageal junction (GEJ) cancer, comprising both oesophageal (EAC) and junctional gastric adenocarcinomas, has increased dramatically in Western countries, correlating with a decrease in non-cardia gastric cancer (GC). A better understanding of the origin and pathogenesis of these cancers may allow for improved cancer prevention, detection and treatment. GEJ adenocarcinomas include tumours classified in the past as either oesophageal or gastric in origin. Adenocarcinoma located just above the GEJ (ie, EAC) was for many years viewed as a distinct entity from GC. This view followed the strong association of EAC with Barrett’s Oesophagus (BE), a metaplastic condition of the lower oesophagus which was viewed as a transdifferentiation of normal squamous epithelium to an intestinalised mucosa in the setting of gastric acid reflux. This assumption of a squamous origin of EAC led to (1) an extensive programme of surveillance of BE patients,(2) the inclusion of oesophageal squamous (ESCC) and adenocarcinoma (EAC) together in some clinical trials and (3) a clear distinction of EAC from GC. We propose here to rethink this approach based on novel insights on the origins and pathogenesis of GEJ cancer. New data supporting a gastric origin of EAC/BE have emerged in recent years from both deep analysis of human samples and with experimental results from human derived cells and mouse models. The hypothesis that BE originates in the gastric cardia was proposed in 2012, based on findings in lineage tracing studies in a BE (L2-IL-1b) mouse model, which recapitulates the histologic progression from oesophagitis to dysplasia. 1 Lineage tracing allows for the genetic definition and tracking of stem cells and their progeny and can help determine the cellular origin of neoplasms. Subsequently, The Cancer Genome Atlas Research Network (TCGA) in 2017 demonstrated in comprehensive molecular genomic profiling of both oesophageal and GCs the distinct features of the two histological subtypes of oesophageal cancer, EAC and ESCC, with ESCC showing much greater similarity to head and neck SCC. Furthermore, joint analysis of EAC and GC could not identify features clearly demarcating EAC from the chromosomal instability (CIN) class of GC, suggesting a shared origin. 2 By contrast, variants of GC that are more common in the non-cardia regions of the stomach including tumours with microsatellite instability, Epstein-Barr virus infection or the diffuse histologic type are less common in GCs localised to the cardia and in EAC. Genetic results from TCGA are consistent with recent epigenetic studies of BE relative to normal gastric and oesophageal tissues, which also demonstrated evidence for a gastric origin to BE. 3 Furthermore, a recent study utilising comprehensive single-cell transcriptomic profiling, in silico lineage tracing, mutation analyses from human tissues spanning the proximal stomach to squamous oesophagus healthy and diseased donors, showed that BE originates from gastric cardia progenitors through distinct transcriptional programmes. 4 This latter study also experimentally determined the capacity of organoid cultures of human gastric tissue to differentiate into BE. Indeed, this emerging view of BE/EAC as originating from gastric tissue is consistent with key pathologic findings that BE always begins at the very distal oesophagus, contiguous with the gastric cardia, and that BE comprises a mosaic of gastric and intestinal cell types which is largely indistinguishable from intestinal metaplasia in the stomach. 5 This new thinking regarding the relationship of EAC echoes the original descriptions of …
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影响因子：
28.2
作者：
Pectasides E;Stachler MD;Derks S;Liu Y;Maron S;Islam M;Alpert L;Kwak H;Kindler H;Polite B;Sharma MR;Allen K;O'Day E;Lomnicki S;Maranto M;Kanteti R;Fitzpatrick C;Weber C;Setia N;Xiao SY;Hart J;Nagy RJ;Kim KM;Choi MG;Min BH;Nason KS;O'Keefe L;Watanabe M;Baba H;Lanman R;Agoston AT;Oh DJ;Dunford A;Thorner AR;Ducar MD;Wollison BM;Coleman HA;Ji Y;Posner MC;Roggin K;Turaga K;Chang P;Hogarth K;Siddiqui U;Gelrud A;Ha G;Freeman SS;Rhoades J;Reed S;Gydush G;Rotem D;Davison J;Imamura Y;Adalsteinsson V;Lee J;Bass AJ;Catenacci DV
通讯作者：
Catenacci DV
影响因子：
50.3
作者：
Quante M;Bhagat G;Abrams JA;Marache F;Good P;Lee MD;Lee Y;Friedman R;Asfaha S;Dubeykovskaya Z;Mahmood U;Figueiredo JL;Kitajewski J;Shawber C;Lightdale CJ;Rustgi AK;Wang TC
通讯作者：
Wang TC
影响因子：
64.8
作者：
Cancer Genome Atlas Research Network;Analysis Working Group: Asan University;BC Cancer Agency;Brigham and Women’s Hospital;Broad Institute;Brown University;Case Western Reserve University;Dana-Farber Cancer Institute;Duke University;Greater Poland Cancer Centre;Harvard Medical School;Institute for Systems Biology;KU Leuven;Mayo Clinic;Memorial Sloan Kettering Cancer Center;National Cancer Institute;Nationwide Children’s Hospital;Stanford University;University of Alabama;University of Michigan;University of North Carolina;University of Pittsburgh;University of Rochester;University of Southern California;University of Texas MD Anderson Cancer Center;University of Washington;Van Andel Research Institute;Vanderbilt University;Washington University;Genome Sequencing Center: Broad Institute;Washington University in St. Louis;Genome Characterization Centers: BC Cancer Agency;Broad Institute;Harvard Medical School;Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University;University of North Carolina;University of Southern California Epigenome Center;University of Texas MD Anderson Cancer Center;Van Andel Research Institute;Genome Data Analysis Centers: Broad Institute;Brown University:;Harvard Medical School;Institute for Systems Biology;Memorial Sloan Kettering Cancer Center;University of California Santa Cruz;University of Texas MD Anderson Cancer Center;Biospecimen Core Resource: International Genomics Consortium;Research Institute at Nationwide Children’s Hospital;Tissue Source Sites: Analytic Biologic Services;Asan Medical Center;Asterand Bioscience;Barretos Cancer Hospital;BioreclamationIVT;Botkin Municipal Clinic;Chonnam National University Medical School;Christiana Care Health System;Cureline;Duke University;Emory University;Erasmus University;Indiana University School of Medicine;Institute of Oncology of Moldova;International Genomics Consortium;Invidumed;Israelitisches Krankenhaus Hamburg;Keimyung University School of Medicine;Memorial Sloan Kettering Cancer Center;National Cancer Center Goyang;Ontario Tumour Bank;Peter MacCallum Cancer Centre;Pusan National University Medical School;Ribeirão Preto Medical School;St. Joseph’s Hospital &Medical Center;St. Petersburg Academic University;Tayside Tissue Bank;University of Dundee;University of Kansas Medical Center;University of Michigan;University of North Carolina at Chapel Hill;University of Pittsburgh School of Medicine;University of Texas MD Anderson Cancer Center;Disease Working Group: Duke University;Memorial Sloan Kettering Cancer Center;National Cancer Institute;University of Texas MD Anderson Cancer Center;Yonsei University College of Medicine;Data Coordination Center: CSRA Inc.;Project Team: National Institutes of Health
通讯作者：
Project Team: National Institutes of Health
影响因子：
9.8
作者：
Verbeek, Romy E.;Leenders, Max;Siersema, Peter D.
通讯作者：
Siersema, Peter D.
影响因子：
9.6
作者：
BARRETT, NR
通讯作者：
BARRETT, NR