Department of Pathology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
Pathol Int. 2011 May;61(5):281-9. doi: 10.1111/j.1440-1827.2011.02650.x. Epub 2011 Mar 17.
Amino acid transporters are essential for maintenance and proliferation of both normal and transformed cells. In the present study, L-type amino-acid transporter 1 (LAT1) immunoreactive expression was investigated in gastric carcinomas, in comparison with gastric adenomas and non-neoplastic lesions, using our recently developed novel monoclonal antibody. In a total of 87 cases of advanced gastric cancer, high LAT1 expression was observed in carcinoma cells, predominantly at plasma membranes with greater intensity in non-scirrhous than scirrhous carcinomas. Gastric carcinoma cases with lymph node metastasis showed significantly higher LAT1 expression than cases without lymph node metastasis. A positive correlation with Ki-67 LI was observed and the highly expressing non-scirrhous carcinomas showed a significantly poorer prognosis than the low LAT1 group. Cox hazard test revealed that TNM stage and LAT1 expression were independent prognostic factors in non-scirrhous carcinoma group. Further, a significant poor prognosis was confirmed in high LAT1 expression group, when limited to undifferentiated carcinoma cases excluding scirrhous carcinoma. Lower levels were found in adenomas. In conclusion, LAT 1 expression may be linked with cell proliferation and prognosis of gastric carcinomas, and offers a potential target for future anticancer therapy by inhibitors.
氨基酸转运体对于正常和转化细胞的维持和增殖都是必不可少的。在本研究中,我们使用新开发的单克隆抗体研究了 L 型氨基酸转运体 1(LAT1)在胃癌中的免疫反应性表达,与胃腺瘤和非肿瘤病变进行了比较。在总共 87 例进展期胃癌中,癌细胞中观察到高 LAT1 表达,主要位于质膜上,非硬癌比硬癌的强度更大。有淋巴结转移的胃癌病例的 LAT1 表达明显高于无淋巴结转移的病例。观察到与 Ki-67 LI 的正相关,高表达的非硬癌比低 LAT1 组的预后明显更差。Cox 风险检验显示,TNM 分期和 LAT1 表达是非硬癌组的独立预后因素。此外,当仅限于排除硬癌的未分化癌病例时,在高 LAT1 表达组中证实了预后不良。在腺瘤中发现较低的水平。总之,LAT1 表达可能与胃癌的细胞增殖和预后有关,并为未来通过抑制剂进行抗癌治疗提供了潜在的靶标。