Correlation of high LAT1 expression with the prognosis of endometrioid carcinoma of the uterine corpus
- PDF / 743,027 Bytes
- 7 Pages / 595.276 x 790.866 pts Page_size
- 35 Downloads / 162 Views
ORIGINAL ARTICLE
Correlation of high LAT1 expression with the prognosis of endometrioid carcinoma of the uterine corpus Kimiya Sato 1
&
Morikazu Miyamoto 2 & Masashi Takano 2 & Hitoshi Tsuda 1
Received: 27 December 2019 / Revised: 9 February 2020 / Accepted: 20 February 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract The expression of L-type amino acid transporter 1 (LAT1) has been described to play essential roles in cancer cell growth and survival. To determine the significance of LAT1 in the prognosis of endometrial endometrioid carcinoma, we investigated LAT1 expression in 353 endometrioid carcinoma patients by immunohistochemical analysis using tissue microarray. The tumors in which stained tumor cells made up more than 25% of the tumor were graded as high expression. High expression of LAT1 was detected in 29 (8.2%) of patients. The ratio of high LAT1 expression did not significantly differ by age (< 60 vs. ≥ 60), FIGO stage (stage I/II vs. III/IV), histological grade (grade 1 vs. grade 2/3), or lymph node metastasis (positive vs. negative). However, high LAT1 expression in endometrioid carcinoma was associated with a poorer progression-free survival and overall survival, as per the results of the log-rank test (P = 0.0263 and 0.0404, respectively). Cox univariate and multivariate analyses revealed that high LAT1 expression is an independent marker of poor progression-free survival (hazard ratio = 2.598, P = 0.0137), in addition to a higher age (≥ 60 years vs. < 60 years), FIGO stage (stage III/IV vs. I/II), and histological grade (grade 2/3 vs. grade 1). In conclusion, we demonstrate that LAT1 is associated with a poor prognosis of endometrioid carcinoma of the uterine corpus. Keywords LAT1 . Uterine corpus cancer . Endometrioid carcinoma . Immunohistochemistry
Introduction L-type amino acid transporter 1 (LAT1) is a Na+-independent amino acid transporter that transports large neutral amino acids such as leucine, isoleucine, valine, phenylalanine, tyrosine, tryptophan, methionine, and histidine [1, 2]. LAT1 requires covalent association with the heavy chain of the 4F2 cell-surface antigen (CD98) for its functional expression in the plasma membrane [1, 2]. Previous studies have shown that LAT1 is highly expressed in many human cancers and is associated with a more aggressive cancer biology [3–18]. LAT1 This article is part of the Topical Collection on Quality in Pathology * Kimiya Sato [email protected] 1
Department of Basic Pathology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan
2
Department of Obstetrics and Gynecology, National Defense Medical College, Tokorozawa, Japan
provides cancer cells with the essential amino acids required for protein synthesis and for stimulation of the growth of cancer cells via the mammalian target of rapamycin (mTOR) pathway [19, 20]. It has been suggested that LAT1 inhibitors such as 2-aminobicyclio-(2,2,1)-heptane-2-carboxylic acid (BCH) may be useful as an adjuvant therapeutic in multiple cancers [20–2
Data Loading...
