Nam Kyung Han, Kim Min A, Choe Gheeyoung, Kim Woo Ho, Lee Hye Seung
Department of Pathology, Seoul National University Bundang Hospital, 173-82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-707, Korea.
Gastric Cancer. 2014 Oct;17(4):610-20. doi: 10.1007/s10120-013-0324-0. Epub 2013 Dec 13.
We investigated the roles of Lethal giant larvae 2 (Lgl2), an epithelial cell polarity protein, during gastric carcinogenesis and gastric cancer (GC) progression and evaluated the correlation of Lgl2 with epithelial-mesenchymal transition (EMT) markers.
Lgl2 protein and mRNA expression were determined by immunohistochemistry and mRNA in situ hybridization in a large series of GC and preneoplastic lesions. Additionally, expression of 7 EMT markers was examined by immunohistochemistry.
Loss of membrane Lgl2 staining in GC was observed in 347 of 409 GCs. Lgl2 loss was associated with diffuse histological type (P < 0.001), advanced stage (P = 0.021), and worse prognosis (P = 0.047). Furthermore, Lgl2 loss correlated with reduced E-cadherin expression (P < 0.01) and increased expression of vimentin (P < 0.01). Combined analysis of Lgl2 and the EMT markers, S100A4 and MMP2, improved predictions of patient outcomes. During gastric carcinogenesis, membrane expression of Lgl2 was progressively lost in 4 % of normal mucosa, 75 % of intestinal metaplasia, 58 % of gastric dysplasia, 69 % of intestinal type GC, and 96 % of diffuse type GC.
Our results suggest that Lgl2 loss occurs at an early stage of gastric carcinogenesis and contributes to GC progression.
我们研究了上皮细胞极性蛋白致死性巨幼虫2（Lgl2）在胃癌发生和胃癌（GC）进展过程中的作用，并评估了Lgl2与上皮-间质转化（EMT）标志物的相关性。
通过免疫组织化学和mRNA原位杂交检测了大量GC及癌前病变中Lgl2蛋白和mRNA的表达。此外，通过免疫组织化学检测了7种EMT标志物的表达。
在409例GC中，有347例观察到GC中膜Lgl2染色缺失。Lgl2缺失与弥漫性组织学类型（P < 0.001）、晚期（P = 0.021）及预后较差（P = 0.047）相关。此外，Lgl2缺失与E-钙黏蛋白表达降低（P < 0.01）及波形蛋白表达增加（P < 0.01）相关。Lgl2与EMT标志物S100A4和MMP2的联合分析改善了对患者预后的预测。在胃癌发生过程中，Lgl2的膜表达在4%的正常黏膜、75%的肠化生、58%的胃发育异常、69%的肠型GC和96%的弥漫型GC中逐渐丧失。
我们的结果表明，Lgl2缺失发生在胃癌发生的早期阶段，并促进了GC的进展。
