The clinical significance of L-type amino acid transporter 1 (LAT1) expression remains unclear, whereas many experimental studies have demonstrated that LAT1 is associated with the proliferation of cancer cells. The purpose of this study was to evaluate the prognostic value of LAT1 in patients with nonsmall cell lung cancer (NSCLC). A total of 321 consecutive patients with completely resected pathologic stage I -III NSCLC were retrospectively reviewed. Expression of LAT1 and proliferative activity, as determined by the Ki-67 labelling index, was also evaluated immunohistochemically and correlated with the prognosis of patients who underwent complete resection of the tumour. Expression of LAT1 was positive in 163 patients (51%) (29% of adenocaricnoma (58 of 200 patients), 91% of squamous cell carcinoma (91 of 100 patients), and 67% of large cell carcinoma (14 of 21 patients)). The 5-year survival rate of LAT1-positive patients (51.8%) was significantly worse than that of LAT1-negative patients (87.8%; Po0.001). L-type amino acid transporter 1 expression was significantly associated with lymph node metastasis and disease stage. Multivariate analysis confirmed that positive expression of LAT1 was an independent factor for predicting a poor prognosis. There was a significant correlation between LAT1 expression and Ki-67 labelling index. LAT1 expression is a promising pathological factor to predict the prognosis in patients with resectable stage I -III NSCLC.

Metabolic response by F-FDG was effective in predicting efficacy and survival at 1 month after nivolumab treatment.

No abstract

No abstract

The significance of L-type amino acid transporter (LAT) 1 expression remains unclear in the metastatic process of human neoplasms, whereas experimental studies have demonstrated that LAT1 is associated with the metastatic process of cancer cells. We compared the immunohistochemical expression of LAT1 and CD98 between the primary site and a concordant pulmonary metastatic site in 93 cancer patients, all of whom had undergone thoracotomy. LAT1, CD98, Ki-67 labeling index, vascular endothelial growth factor (VEGF), CD31, and CD34 were analyzed by immunohistochemical staining in the resected tumors of 93 cancer patients: 45 colon cancers; nine breast cancers; eight head and neck cancers; 11 genital cancers; 14 soft-tissue sarcomas; and six other cancers. The expression of these markers was significantly higher in the metastatic sites than in the primary sites. In total, the positive rates of LAT1, CD98, Ki-67, VEGF, CD31, and CD34 were 40, 24, 56, 41, 45, and 39%, respectively, in the primary sites and 65, 45, 84, 67, 73, and 61%, respectively, in the metastatic sites. LAT1 expression was closely correlated with CD98 expression, angiogenesis, and cell proliferation. The association between LAT1 and CD98 expression was strongest in the primary and metastatic sites. The present study suggests that overexpression of LAT1 and CD98 has an important role to play in the metastatic process of variable human neoplasms. (1,2) Amino acid transporter system l is a Na-independent large and neutral amino acid transport agency.(1,3) l-type amino acid transporter (LAT) 1 is an l-type amino acid transporter that transports large neutral amino acids, such as leucine, isoleucine, valine, phenylalanine, tyrosine, tryptophan, methionine, and histidine. (2)(3)(4) LAT1 requires a covalent association with the heavy chain of the 4F2 cell surface antigen (CD98) for its functional expression in plasma membrane.(3) Previous studies have shown LAT1 to be expressed highly in proliferating tissues, many tumor cell lines (T24 bladder carcinoma cells, RERF-LC-MA lung small-cell carcinoma cells, and HeLa uterine cervical carcinoma cells) and primary human tumors.(4) Recent studies have demonstrated the overexpression of LAT1 in lung cancer and esophageal carcinoma.(5-7) Positive expression of LAT1 is reported to be a significant factor in predicting poor prognosis in non-small cell lung cancer (NSCLC), and tends to increase from low-grade to high-grade neuroendocrine tumors of the lung.(7,8) Nakanishi et al. reported that the cooperative expression of LAT1 and CD98 is significantly correlated with both overall and disease-free survival rates in transitional-cell carcinoma of the upper urinary tract.(9) Nawashiro et al. reported that overall immunoreactivity for LAT1 correlates well with the prognosis of patients with astrocytic tumors, and high CD98 immunoreactivity also correlates with high LAT1 expression.(10) An experimental study demonstrated that LAT1 expression is closely related to tumor cell growth of liver metastases in a rat model, (11) a...