Department of Surgery, Tohoku University Hospital, Miyagi, Japan.
Department of Pathology, Tohoku University Hospital, Miyagi, Japan.
Pathol Int. 2020 Jun;70(6):355-363. doi: 10.1111/pin.12922. Epub 2020 Mar 15.
Barrett's esophagus (BE) is a consequence of gastroesophageal reflux disease and is predisposed to esophageal adenocarcinoma (EAC). EAC is an exemplar model of inflammation-associated cancer. Glucocorticoids suppress inflammation through glucocorticoid receptor (GR) and serum- and glucocorticoid-induced kinase-1 (Sgk1) expressions. Therefore, we immunolocalized GR and Sgk1 in EAC and the adjacent BE tissues and studied their association with clinical disease course in 87 patients with EAC who underwent surgical resection (N = 58) or endoscopic submucosal dissection (N = 29). Low GR and Sgk1 expressions in adjacent BE tissues were associated with adverse clinical outcomes (P = 0.0008 and 0.034, respectively). Patients with low Sgk1 expression in EAC cells exhibited worse overall survival (P = 0.0018). In multivariate Cox regression analysis, low GR expression in the adjacent nonmalignant BE tissues was significantly associated with worse overall survival (P = 0.023). The present study indicated that evaluation of GR and Sgk1 expressions in both the EAC cells and adjacent nonmalignant BE tissues could help to predict clinical outcomes following endoscopic and surgical treatments. In particular, the GR status in BE tissues adjacent to EAC was an independent prognostic factor.
巴雷特食管（BE）是胃食管反流病的后果，易患食管腺癌（EAC）。EAC 是炎症相关癌症的典范模型。糖皮质激素通过糖皮质激素受体（GR）和血清和糖皮质激素诱导激酶-1（Sgk1）的表达来抑制炎症。因此，我们在 EAC 和相邻的 BE 组织中免疫定位了 GR 和 Sgk1，并在 87 名接受手术切除（N=58）或内镜黏膜下剥离术（N=29）的 EAC 患者中研究了它们与临床疾病过程的关系。相邻 BE 组织中低 GR 和 Sgk1 表达与不良临床结局相关（P=0.0008 和 0.034，分别）。EAC 细胞中低 Sgk1 表达的患者总生存率较差（P=0.0018）。多变量 Cox 回归分析表明，相邻非恶性 BE 组织中低 GR 表达与总生存率降低显著相关（P=0.023）。本研究表明，评估 EAC 细胞和相邻非恶性 BE 组织中 GR 和 Sgk1 的表达有助于预测内镜和手术治疗后的临床结局。特别是 EAC 周围 BE 组织中的 GR 状态是一个独立的预后因素。
