LKB1 protein expression in neuroendocrine tumors of the lung
LKB1 protein expression in neuroendocrine tumors of the lung
复制标题
DOI：
10.1111/j.1440-1827.2007.02194.x
复制
发表时间：
2008-02-01
影响因子：
2.2
通讯作者：
Nakatani, Yukio
中科院分区：
文献类型：
--
作者：
Amin, Randa Mahmoud Sobhi;Hiroshima, Kenzo;Nakatani, Yukio
在最近对肺部病变中 LKB1 基因异常的研究中，发现支气管上皮的正常神经内分泌 (NE) 细胞中 LKB1 蛋白强表达。由于LKB1作为抑癌基因发挥作用，因此研究了LKB1表达的改变是否与各种级别的肺NE肿瘤的发生有关。对总共 68 例原发性肺 NE 肿瘤进行了 LKB1 免疫组织化学检查，其中包括 30 例小细胞肺癌 (SCLC)、23 例大细胞神经内分泌癌 (LCNEC)、2 例非典型类癌和 13 例典型类癌。 LKB1 蛋白表达缺失或低表达（< 20% 免疫反应性细胞）在高级别 NE 肿瘤（SCLC 和 LCNEC；45/53，84.9%）中比在典型和非典型类癌（3/15；20%）中更常见。高级别NE肿瘤与类癌组之间LKB1免疫反应性差异有统计学意义（P<0.0001）。总之，肺高级 NE 肿瘤中 LKB1 表达显着降低表明 LKB1 失活可能在其肿瘤发生中发挥作用。尽管之前的一些研究表明 SCLC 中 LKB1 存在罕见的遗传改变，但仍需要进一步的研究，包括分析其他 NE 肿瘤并关注 LKB1 基因的表观遗传异常。
During a recent investigation of LKB1 gene abnormality in lung lesions, strong expression of LKB1 protein in normal neuroendocrine (NE) cells of the bronchial epithelium was found. Because LKB1 functions as a tumor suppressor gene, the question of whether alteration of LKB1 expression is related to the development of pulmonary NE tumors of various grades was investigated. LKB1 immunohistochemistry was examined in a total of 68 primary pulmonary NE tumors consisting of 30 specimens of small cell lung carcinoma (SCLC), 23 large cell neuroendocrine carcinomas (LCNEC), two atypical carcinoids, and 13 typical carcinoids. Loss or low expression (< 20% immunoreactive cells) of LKB1 protein expression was more frequently observed in high-grade NE tumors (SCLC and LCNEC; 45/53, 84.9%) than in typical and atypical carcinoids (3/15; 20%). The difference in LKB1 immunoreactivity between the high-grade NE tumors and the carcinoid group was statistically significant (P < 0.0001). In conclusion, marked reduction of LKB1 expression in high-grade NE tumors of the lung suggests a possible role of LKB1 inactivation in its tumorigenesis. Although a few previous studies indicated rare genetic alterations of LKB1 in SCLC, further studies including analysis of other NE tumors and focusing on epigenetic abnormalities of LKB1 gene are warranted.