nach oben

Virchows Archiv

Erschienen in:

06.03.2020 | Original Article

Correlation of high LAT1 expression with the prognosis of endometrioid carcinoma of the uterine corpus

verfasst von: Kimiya Sato, Morikazu Miyamoto, Masashi Takano, Hitoshi Tsuda

Erschienen in: Virchows Archiv | Ausgabe 3/2020

Einloggen, um Zugang zu erhalten

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.

Kanai Y, Segawa H, Miyamoto K, Uchino H, Takeda E, Endou H (1998) Expression cloning and characterization of a transporter for large neutral amino acids activated by the heavy chain of 4F2 antigen (CD98). J Biol Chem 273:23629–23632CrossRef

Yanagida O, Kanai Y, Chairoungdua A et al (2001) Human L-type amino acid transporter 1 (LAT 1): characterization of function and expression in tumor cell lines. Biochim Biophys Acta 1514:291–302CrossRef

Nawashiro H, Otani N, Shinomiya N, Fukui S, Ooigawa H, Shima K, Matsuo H, Kanai Y, Endou H (2006) L-type amino acid transporter 1 as a potential molecular target in human astrocytic tumors. Int J Cancer 119:484–492CrossRef

Nakanishi K, Ogata S, Matsuo H et al (2007) Expression of LAT1 predicts risk of progression of transitional cell carcinoma of the upper urinary tract. Virchows Arch 451:681–690CrossRef

Kaira K, Oriuchi N, Imai H et al (2008) Prognostic significance of L-type amino acid transporter 1 expression in resectable stage I-III nonsmall cell lung cancer. Br J Cancer 98:742–748CrossRef

Sakata T, Ferdous G, Tsuruta T, Satoh T, Baba S, Muto T, Ueno A, Kanai Y, Endou H, Okayasu I (2009) L-type amino-acid transporter 1 as a novel biomarker for high-grade malignancy in prostate cancer. Pathol Int 59:7–18CrossRef

Liang Z, Cho HT, Williams L et al (2011) Potential biomarker of L-type amino acid transporter 1 in breast cancer progression. Nucl Med Mol Imaging 45:93–102CrossRef

Ichinoe M, Mikami T, Yoshida T, Igawa I, Tsuruta T, Nakada N, Anzai N, Suzuki Y, Endou H, Okayasu I (2011) High expression of L-type amino-acid transporter 1 (LAT1) in gastric carcinomas: comparison with non-cancerous lesions. Pathol Int 61:281–289CrossRef

Uno K, Kuwabara H, Terado Y, Kojima K, Kawakami T, Kamma H, Sakurai H, Sakamoto A, Kurata A (2011) Divergent expression of L-type amino acid transporter 1 during uterine cervical carcinogenesis. Hum Pathol 42:1660–1666CrossRef

10.

Kaira K, Sunose Y, Arakawa K et al (2012) Prognostic significance of L-type amino-acid transporter 1 expression in surgically resected pancreatic cancer. Br J Cancer 107:632–638CrossRef

11.

Kaira K, Sunose Y, Ohshima Y et al (2013) Clinical significance of L-type amino acid transporter 1 expression as a prognostic marker and potential of new targeting therapy in biliary tract cancer. BMC Cancer 13:482CrossRef

12.

Toyoda M, Kaira K, Ohshima Y, Ishioka NS, Shino M, Sakakura K, Takayasu Y, Takahashi K, Tominaga H, Oriuchi N, Nagamori S, Kanai Y, Oyama T, Chikamatsu K (2014) Prognostic significance of amino-acid transporter expression (LAT1, ASCT2, and xCT) in surgically resected tongue cancer. Br J Cancer 110:2506–2513CrossRef

13.

Isoda A, Kaira K, Iwashina M et al (2014) Expression of L-type amino acid transporter 1 (LAT1) as a prognostic and therapeutic indicator in multiple myeloma. Cancer Sci 105:1496–1502CrossRef

14.

Hayase S, Kumamoto K, Saito K et al (2017) L-type amino acid transporter 1 expression is upregulated and associated with cellular proliferation in colorectal cancer. Oncol Lett 14:7410–7416PubMedPubMedCentral

15.

Kaji M, Kabir-Salmani M, Anzai N et al (2010) Properties of L-type amino acid transporter 1 in epidermal ovarian cancer. Int J Gynecol Cancer 20:329–336CrossRef

16.

Kaira K, Nakamura K, Hirakawa T, Imai H, Tominaga H, Oriuchi N, Nagamori S, Kanai Y, Tsukamoto N, Oyama T, Asao T, Minegishi T (2015) Prognostic significance of L-type amino acid transporter 1 (LAT1) expression in patients with ovarian tumors. Am J Transl Res 7:1161–1171PubMedPubMedCentral

17.

Betsunoh H, Fukuda T, Anzai N et al (2013) Increased expression of system large amino acid transporter (LAT)-1 mRNA is associated with invasive potential and unfavorable prognosis of human clear cell renal cell carcinoma. BMC Cancer 13:509CrossRef

18.

Sato K, Miyamoto M, Takano M, Furuya K, Tsuda H (2019) Significant relationship between the LAT1 expression pattern and chemoresistance in ovarian clear cell carcinoma. Virchows Arch 474:701–710CrossRef

19.

Fuchs BC, Bode BP (2005) Amino acid transporters ASCT2 and LAT1 in cancer: partners in crime? Semin Cancer Biol 15:254–266CrossRef

20.

Wang Q, Holst J (2015) L-type amino acid transport and cancer: targeting the mTORC1 pathway to inhibit neoplasia. Am J Cancer Res 5:1281–1294PubMedPubMedCentral

21.

Yamauchi K, Sakurai H, Kimura T, Wiriyasermkul P, Nagamori S, Kanai Y, Kohno N (2009) System L amino acid transporter inhibitor enhances anti-tumor activity of cisplatin in a head and neck squamous cell carcinoma cell line. Cancer Lett 276:95–101CrossRef

22.

Imai H, Kaira K, Oriuchi N et al (2010) Inhibition of L-type amino acid transporter 1 has antitumor activity in non-small cell lung cancer. Anticancer Res 30:4819–4828PubMed

23.

Fan X, Ross DD, Arakawa H, Ganapathy V, Tamai I, Nakanishi T (2010) Impact of system L amino acid transporter 1 (LAT1) on proliferation of human ovarian cancer cells: a possible target for combination therapy with anti-proliferative aminopeptidase inhibitors. Biochem Pharmacol 80:811–818CrossRef

24.

Jemal A, Bray F, Center MM et al (2011) Global cancer statistics. CA Cancer J Clin 61:69–90CrossRef

25.

Kurman RJ, Carcangiu ML, Herrington CS, Young RH (2014) WHO classification of tumours of female reproductive organs. IARC Press, Lyon

26.

Watanabe J, Yokoyama Y, Futagami M et al (2014) L-type amino acid transporter 1 expression increases in well-differentiated but decreases in poorly differentiated endometrial endometrioid adenocarcinoma and shows an inverse correlation with p53 expression. Int J Gynecol Cancer 24:659–663CrossRef

27.

Marshall AD, van Geldermalsen M, Otte NJ, Anderson LA, Lum T, Vellozzi MA, Zhang BK, Thoeng A, Wang Q, Rasko JE, Holst J (2016) LAT1 is a putative therapeutic target in endometrioid endometrial carcinoma. Int J Cancer 139:2529–2539CrossRef

28.

Finger DC, Blenis J (2004) Target of rapamycin (TOR): an integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression. Oncogene 23:3151–3171CrossRef

29.

Wang X, Proud CG (2006) The mTOR pathway in the control of protein synthesis. Physiology (Bathesda) 21:362–369CrossRef

30.

Byfield MP, Murray JT, Backer JM (2005) hVps34 is a nutrient-regulated lipid kinase required for activation of p70 S6 kinase. J Biol Chem 280:33076–33082CrossRef

31.

Nobukuni T, Joaquin M, Roccio M, Dann SG, Kim SY, Gulati P, Byfield MP, Backer JM, Natt F, Bos JL, Zwartkruis FJ, Thomas G (2005) Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase. Proc Natl Acad Sci U S A 102:14238–14243CrossRef

32.

McCarty MF (2001) Mortality from Western cancers rose dramatically among African-Americans during the 20th century: are dietary animal products to blame? Med Hypotheses 57:169–174CrossRef

33.

Bravi F, Bertuccio P, Turati F, Serraino D, Edefonti V, Dal Maso L, Decarli A, Montella M, Zucchetto A, la Vecchia C, Bosetti C, Ferraroni M (2015) Nutrient-based dietary patterns and endometrial cancer risk: an Italian case-control study. Cancer Epidemiol 39:66–72CrossRef

34.

O’Connell TM (2013) The complex role of branched chain amino acids in diabetes and cancer. Metabolites 3:931–945CrossRef

35.

Oda K, Hosoda N, Endo H, Saito K, Tsujihara K, Yamamura M, Sakata T, Anzai N, Wempe MF, Kanai Y, Endou H (2010) L-type amino acid transporter 1 inhibitors inhibit tumor cell growth. Cancer Sci 101:173–179CrossRef

36.

Cancer Genome Atlas Research Network, Kandoth C, Schultz N, Cherniack AD et al (2013) Integrated genomic characterization of endometrial carcinoma. Nature 497:67–73CrossRef

Titel: Correlation of high LAT1 expression with the prognosis of endometrioid carcinoma of the uterine corpus
verfasst von: Kimiya Sato
Morikazu Miyamoto
Masashi Takano
Hitoshi Tsuda
Publikationsdatum: 06.03.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: Virchows Archiv / Ausgabe 3/2020
Print ISSN: 0945-6317
Elektronische ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-020-02781-0

Springer Medizin

Correlation of high LAT1 expression with the prognosis of endometrioid carcinoma of the uterine corpus

Abstract

Neu im Fachgebiet Pathologie

Molekularpathologische Untersuchungen im Wandel der Zeit

Vergleichende Pathologie in der onkologischen Forschung

Gastrointestinale Stromatumoren

Personalisierte Medizin in der Onkologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2020

Pulmonary arterial thrombosis as an important complication of COVID-19 pulmonary disease: letter to the editor

Germany’s first COVID-19 deceased: a 59-year-old man presenting with diffuse alveolar damage due to SARS-CoV-2 infection

In this issue

Chemotherapy-associated foam cell aggregates as a prognostic factor in patients with pelvic high-grade serous carcinoma receiving neo-adjuvant chemotherapy

The evolution of pulmonary pathology in fatal COVID-19 disease: an autopsy study with clinical correlation

Unlocking the lockdown of science and demystifying COVID-19: how autopsies contribute to our understanding of a deadly pandemic

Neu im Fachgebiet Pathologie

Molekularpathologische Untersuchungen im Wandel der Zeit

Vergleichende Pathologie in der onkologischen Forschung

Gastrointestinale Stromatumoren

Personalisierte Medizin in der Onkologie