Kaira Kyoichi, Oriuchi Noboru, Imai Hisao, Shimizu Kimihiro, Yanagitani Noriko, Sunaga Noriaki, Hisada Takeshi, Kawashima Osamu, Iijima Hironobu, Ishizuka Tamotsu, Kanai Yoshikatsu, Endou Hitoshi, Nakajima Takashi, Mori Masatomo
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Showa-machi, Maebashi, Gunma 371-8511, Japan.
Pathol Res Pract. 2008;204(8):553-61. doi: 10.1016/j.prp.2008.02.003. Epub 2008 Apr 28.
Amino acid transport systems play an important role in cellular proliferation. L-type amino acid transporter 1 (LAT1) has been associated with tumor growth, and is highly expressed in the established tumor cell lines and primary human neoplasms. In this study, we investigated the expression of LAT1 to evaluate the malignant potential and prognostic significance in neuroendocrine (NE) tumors of the lung. Twenty-one surgically resected, large cell neuroendocrine carcinomas (LCNEC), 13 small cell lung cancers (SCLC), five atypical carcinoids (AC), and 10 typical carcinoids (TC) were enrolled in the study. LAT1 expression and Ki-67 labeling index of the NE tumors were analyzed by immunohistochemical staining. LAT1 was overexpressed in 52.4% of the LCNEC, in 46.2% of the SCLC, and in 25% of the AC. LAT1 expression in LCNEC was significantly associated with lymph node metastasis and poor outcome. Moreover, a significant correlation was found between LAT1 expression and Ki-67 in both LCNEC and SCLC. Expression of LAT1 tended to increase from low-grade to high-grade NE tumors. The present results suggest that LAT1 may play a significant role in cellular proliferation, lymph node metastasis, and poor outcome in patients with NE tumors of the lung.
氨基酸转运系统在细胞增殖中起重要作用。L型氨基酸转运体1(LAT1)与肿瘤生长相关,在已建立的肿瘤细胞系和原发性人类肿瘤中高表达。在本研究中,我们调查了LAT1的表达,以评估其在肺神经内分泌(NE)肿瘤中的恶性潜能和预后意义。本研究纳入了21例手术切除的大细胞神经内分泌癌(LCNEC)、13例小细胞肺癌(SCLC)、5例非典型类癌(AC)和10例典型类癌(TC)。通过免疫组织化学染色分析NE肿瘤的LAT1表达和Ki-67标记指数。LAT1在52.4%的LCNEC、46.2%的SCLC和25%的AC中过表达。LCNEC中LAT1的表达与淋巴结转移和不良预后显著相关。此外,在LCNEC和SCLC中均发现LAT1表达与Ki-67之间存在显著相关性。从低级别到高级别NE肿瘤,LAT1的表达呈上升趋势。目前的结果表明,LAT1可能在肺NE肿瘤患者的细胞增殖、淋巴结转移和不良预后中起重要作用。