*Division of Medical Life Sciences, Department of Pathologic Analysis, Graduate School of Health Sciences, and †Department of Obstetrics and Gynecology, Graduate School of Medicine, Hirosaki University, Hirosaki; ‡Department of Pathology, Kitasato University School of Medicine, Sagamihara; and §J-Pharma Co, Ltd; and ∥Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, Japan.
Int J Gynecol Cancer. 2014 May;24(4):659-63. doi: 10.1097/IGC.0000000000000123.
The aims of this study were to determine whether the altered L-type amino acid transporter 1 (LAT1) expression is related to clinicopathologic factors, expressions of Ki-67, p53, estrogen receptor, and progesterone receptor and clarify the significance of LAT1 as a prognostic factor and the novel possibility of using it to treat endometrial endometrioid adenocarcinoma.
The LAT1 expression was analyzed immunohistochemically in atrophic (6 cases), secretory phase (6 cases), proliferative phase endometria (6 cases), atypical hyperplasia (6 cases), and endometrioid adenocarcinoma (26 well-differentiated [G1], 17 moderately differentiated, and 11 poorly differentiated [G3] adenocarcinoma patients).
The LAT1 expression was observed in the cell membrane. Its expression increased in the atrophic, secretory, and proliferative phases of the endometrium in that order. There was no difference between the proliferative phase endometrium, atypical hyperplasia, and G1 adenocarcinoma. The LAT1 expression in G1 adenocarcinoma was significantly higher than that in G3 adenocarcinoma. The LAT1 expression was inversely correlated with p53 expression but not with those of Ki-67, estrogen receptor, or progesterone receptor.
It is suggested that the significance of LAT1 as a prognostic factor is low because LAT expression was low in G3 adenocarcinoma, not correlated with the International Federation of Gynecology and Obstetrics stage and proliferative activity and inversely correlated with p53. The LAT1 inhibitors can be used as anticancer drugs for G1 and moderately differentiated adenocarcinoma that express high LAT1.
本研究旨在确定 L 型氨基酸转运蛋白 1（LAT1）表达的改变是否与临床病理因素、Ki-67、p53、雌激素受体和孕激素受体的表达有关，并阐明 LAT1 作为预后因素的意义，以及将其用于治疗子宫内膜子宫内膜样腺癌的新可能性。
采用免疫组织化学方法检测 6 例萎缩期、6 例分泌期、6 例增生期子宫内膜、6 例不典型增生和 26 例分化良好（G1）、17 例中度分化和 11 例低分化（G3）子宫内膜样腺癌患者的 LAT1 表达。
LAT1 表达位于细胞膜，其表达顺序为萎缩期、分泌期和增生期逐渐增加。增生期子宫内膜、不典型增生和 G1 腺癌之间无差异。G1 腺癌的 LAT1 表达明显高于 G3 腺癌。LAT1 表达与 p53 表达呈负相关，与 Ki-67、雌激素受体或孕激素受体表达无关。
LAT1 作为预后因素的意义较低，因为 G3 腺癌中 LAT 表达较低，与国际妇产科联合会分期、增殖活性无关，与 p53 表达呈负相关。LAT1 抑制剂可作为高 LAT1 表达的 G1 和中度分化腺癌的抗癌药物。
