Testa Ugo, Castelli Germana, Pelosi Elvira
Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00141 Rome, Italy.
Medicines (Basel). 2017 Sep 14;4(3):67. doi: 10.3390/medicines4030067.
Esophageal cancer (EC) is the eighth most common cancer and is the sixth leading cause of death worldwide. The incidence of histologic subtypes of EC, esophageal adenocarcinoma (EAC) and esophageal squamous carcinoma (ESCC), display considerable geographic variation. EAC arises from metaplastic Barrett's esophagus (BE) in the context of chronic inflammation secondary to exposure to acid and bile. The main risk factors for developing ESCC are cigarette smoking and alcohol consumption. The main somatic genetic abnormalities showed a different genetic landscape in EAC compared to ESCC. EAC is a heterogeneous cancer dominated by copy number alterations, a high mutational burden, co-amplification of receptor tyrosine kinase, frequent TP53 mutations. The cellular origins of BE and EAC are still not understood: animal models supported a cellular origin either from stem cells located in the basal layer of esophageal epithelium or from progenitors present in the cardia region. Many studies support the existence of cancer stem cells (CSCs) able to initiate and maintain EAC or ESCC. The exact identification of these CSCs, as well as their role in the pathogenesis of EAC and ESCC remain still to be demonstrated. The reviewed studies suggest that current molecular and cellular characterization of EAC and ESCC should serve as background for development of new treatment strategies.
食管癌（EC）是全球第八大常见癌症，也是第六大主要死因。食管癌的组织学亚型，即食管腺癌（EAC）和食管鳞癌（ESCC）的发病率呈现出显著的地域差异。EAC起源于因接触酸和胆汁继发慢性炎症背景下的化生巴雷特食管（BE）。发生ESCC的主要危险因素是吸烟和饮酒。与ESCC相比，EAC的主要体细胞遗传异常呈现出不同的遗传格局。EAC是一种异质性癌症，以拷贝数改变、高突变负荷、受体酪氨酸激酶共扩增、频繁的TP53突变为特征。BE和EAC的细胞起源仍不清楚：动物模型支持其细胞起源于位于食管上皮基底层的干细胞或贲门区域的祖细胞。许多研究支持存在能够启动和维持EAC或ESCC的癌症干细胞（CSC）。这些CSC的确切鉴定及其在EAC和ESCC发病机制中的作用仍有待证实。综述研究表明，目前对EAC和ESCC的分子和细胞特征分析应作为开发新治疗策略的背景依据。
