Prognostic significance of amino-acid transporter expression (LAT1, ASCT2, and xCT) in surgically resected tongue cancer.
BACKGROUND
Amino-acid transporters are necessary for the tumour cell growth and survival, and have a crucial role in the development and invasiveness of cancer cells. But, it remains unclear about the prognostic significance of L-type amino-acid transporter 1 (LAT1), system ASC amino-acid transporter-2 (ASCT2), and xCT expression in patients with tongue cancer. We conducted the clinicopathological study to investigate the protein expression of these amino-acid transporters in tongue cancer.


METHODS
Eighty-five patients with surgically resected tongue cancer were evaluated. Tumour sections were stained by immunohistochemistry for LAT1, ASCT2, xCT, 4F2hc/CD98hc (4F2hc), Ki-67, and microvessel density (MVD) determined by CD34, and p53.


RESULTS
L-type amino-acid transporter 1 and 4F2hc were highly expressed in 61% (52 out of 85) and 45% (38 out of 47), respectively. ASC amino-acid transporter-2 and xCT were positively expressed in 59% (50 out of 85) and 21% (18 out of 85), respectively. The expression of both LAT1 and ASCT2 was significantly associated with disease staging, lymph-node metastasis, lymphatic permeation, 4F2hc expression and cell proliferation (Ki-67). xCT expression indicated a significant association with advanced stage and tumour factor. By univariate analysis, disease staging, lymphatic permeation, vascular invasion, LAT1, ASCT2, 4F2hc, and Ki-67 had a significant relationship with overall survival. Multivariate analysis confirmed that LAT1 was an independent prognostic factor for predicting poor prognosis.


CONCLUSIONS
L-type amino-acid transporter 1 and ASCT2 can serve as a significant prognostic factor for predicting worse outcome after surgical treatment and may have an important role in the development and aggressiveness of tongue cancer.
Department of Otolaryngology-Head and Neck Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
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Toyoda
1] Department of Molecular Medicine and Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan [2] Department of Diagnostic Pathology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan [3] Oncology Center, Gunma University Hospital, Maebashi, Gunma, Japan.
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Kaira
Medical Radioisotope Application Group, Quantum Beam Science Directorate, Japan Atomic Energy Agency, Watanuki, Takasaki, Gunma, Japan.
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Ohshima
Medical Radioisotope Application Group, Quantum Beam Science Directorate, Japan Atomic Energy Agency, Watanuki, Takasaki, Gunma, Japan.
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Ishioka
Department of Otolaryngology-Head and Neck Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
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Shino
Department of Otolaryngology-Head and Neck Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
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Sakakura
Department of Otolaryngology-Head and Neck Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
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Takayasu
Department of Otolaryngology-Head and Neck Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
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Takahashi
Department of Molecular Imaging, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
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Tominaga
Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
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Oriuchi
Division of Bio-System Pharmacology, Graduate School of Medicine, Osaka University, Osaka, Japan.
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Nagamori
Division of Bio-System Pharmacology, Graduate School of Medicine, Osaka University, Osaka, Japan.
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Kanai
Department of Diagnostic Pathology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
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Oyama
Department of Otolaryngology-Head and Neck Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
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Chikamatsu
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D026962:Amino Acid Transport System ASC / Q000032:analysis*; D027182:Amino Acid Transport System y+ / Q000032:analysis*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000737:chemistry* / Q000188:drug therapy / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D000077143:Docetaxel; D004338:Drug Combinations; D005260:Female; D027282:Fusion Regulatory Protein 1, Heavy Chain / Q000032:analysis; D006801:Humans; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000032:analysis; D027283:Large Neutral Amino Acid-Transporter 1 / Q000032:analysis*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D009363:Neoplasm Proteins / Q000032:analysis*; D009367:Neoplasm Staging; D010094:Oxonic Acid / Q000008:administration & dosage; D011379:Prognosis; D043823:Taxoids / Q000008:administration & dosage; D005641:Tegafur / Q000008:administration & dosage; D014062:Tongue Neoplasms / Q000098:blood supply / Q000737:chemistry* / Q000188:drug therapy / Q000601:surgery; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D026962:Amino Acid Transport System ASC; D027182:Amino Acid Transport System y+; D014408:Biomarkers, Tumor; D004338:Drug Combinations; D027282:Fusion Regulatory Protein 1, Heavy Chain; D019394:Ki-67 Antigen; D027283:Large Neutral Amino Acid-Transporter 1; D015778:Minor Histocompatibility Antigens; D009363:Neoplasm Proteins; C420506:SLC1A5 protein, human; C545989:SLC3A2 protein, human; C118895:SLC7A11 protein, human; C495901:TP53 protein, human; D043823:Taxoids; D016159:Tumor Suppressor Protein p53; C079198:S 1 (combination); D005641:Tegafur; D000077143:Docetaxel; D010094:Oxonic Acid