Abstract

Abstract Purpose: Amino acid transporters play important roles in cell survival and proliferation. L-Type amino acid transporter 1 (LAT1) is one of the major Na+-independent neutral amino acid transporters. LAT1 has an aspect of oncofetal protein. Recently, high levels of LAT1 expression have been reported in various tumors, such as prostate cancer, pancreas cancer, bile duct cancer, lung cancer and stomach cancer.We revealed LAT1 expression is an independent prognosis marker in stomach cancer, prostate cancer and pancreas cancer. The purpose of the present study was to investigate the LAT1 expression in breast carcinoma and relationship between LAT1 expression and prognosis. Materials & Methods: We enrolled 290 patients with invasive breast carcinoma surgically resected between 2006 and 2010 at Kitasato University Hospital and Toho University Omori Medical Center, Japan. We investigated LAT1 expression in the enrolled breast carcinoma cases by immunohistochemical staining. All cases were divided into two groups, 78 cases of triple negative carcinoma (TNBC) and 212 cases of non-triple negative carcinoma (NTNBC), with immunohistochemistry of estrogen and progesterone receptors and Her2. After LAT1 expression was compared between TNBC and NTNBC, correlations among LAT1 expression, Ki-67 labeling index (LI), CD98 expression, and clinicopathological findings was assessed. Results: TNBC showed significantly higher LAT1 expression than NTNBC. TNBC also showed significantly higher CD98 expression rather than NTNBC. LAT1 expression of extraductal invasive cancer cells was significantly higher than those of intraductal carcinoma cells. A significantly positive correlation was observed between LAT1 expression and CD98 expression. Further, a positive correlation between LAT1 expression and Ki-67 LI was found. Log-rank test in overall breast cancers revealed that high LAT1 expression group showed significantly poor prognosis, compared to low LAT1 group. In NTNBC, high LAT1expression cases possessed poorer prognosis than low LAT1 expression cases. Conclusion: In invasive ductal carcinoma of breast, LAT1 expression has a potential for a prognosis prediction factor. LAT1 offers a potential target for anti-cancer therapy by its inhibitor JPH203 which has been developed by us. Citation Format: Masaaki Ichinoe, Tetsuo Mikami, Kiyomi Hana, Nobuyuki Yanagisawa, Hitoshi Endou, Isao Okayasu, Yoshiki Murakumo. Expression of cancer type amino acid transporter LAT1 is a prognosis prediction factor in breast carcinoma: comparison between triple-negative and non-triple-negative types. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5286. doi:10.1158/1538-7445.AM2015-5286

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