Li Fei, Zhong Zhiyong, Li Rui, Huang Heyu, Wang Lijun, Zheng Donghan, Zhang Daorong
Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang 110001, China.
Zhongguo Fei Ai Za Zhi. 2010 Apr;13(4):317-21. doi: 10.3779/j.issn.1009-3419.2010.04.09.
Human achaete-scute homolog 1 (hASH1) gene plays a critical role in development of the central nervous system, automatic nervous system, adrenal medullary chromaffin cells, thyroid C cells and pulmonary neuroendocrine cells. The aim of this study is to determine hASH1 gene expression in the normal lung tissue and various types of lung tumors, to analyze whether its expression correlated with pulmonary neuroendocrine markers, and to explore the possibility of hASH1 as clinical pathological markers in the neuroendocrine tumors compared with previous neuroendocrine tumor markers.
hASH1, Chromogranin A, Synaptophysin and CD56 expression were examined in lung tumor specimens (lung inflammatory pseudotumor, squamous cell carcinoma, adenocarcinomas, large cell carcinoma, typical carcinoids, atypical carcinoids, large cell neuroendocrine carcinomas and small cell lung carcinoma and corresponding normal lung specimens) using immunohistochemistry (S-P method). Western blot and reverse transcription polymerase chain reaction (RT-PCR) assay were applied to detect the expressions of hASH1 protein and mRNA in lung cancer tissues.
hASH1 expression was positive in 2/16 (12.5%) typical carcinoids, 15/20 (75%) atypical carcinoids, 6/10 (60%) large cell neuroendocrine carcinomas and 31/40 (77.5%) small cell lung carcinoma, respectively, but not in any normal lung tissue (0/10), lung inflammatory pseudotumor (0/49), squamous cell carcinoma (0/30), adenocarcinomas (0/30) or large cell carcinoma (0/20). There was a significant difference in hASH1 expression between typical carcinoids and atypical carcinoids (P < 0.01), but not in large cell neuroendocrine carcinomas and small cell lung carcinoma (P > 0.05). hASH1 expression highly closely correlated with Chromogranin A, Synaptophysin and CD56 expression (P < 0.05).
hASH1 is a new kind of highly specific markers of pulmonary neuroendocrine tumours, and may be applied to clinical pathology diagnosis of the pulmonary neuroendocrine tumors.
人类无翅型MMTV整合位点家族成员1(hASH1)基因在中枢神经系统、自主神经系统、肾上腺髓质嗜铬细胞、甲状腺C细胞及肺神经内分泌细胞的发育中起关键作用。本研究旨在检测hASH1基因在正常肺组织及各类肺肿瘤中的表达,分析其表达是否与肺神经内分泌标志物相关,并与既往神经内分泌肿瘤标志物比较,探讨hASH1作为神经内分泌肿瘤临床病理标志物的可能性。
采用免疫组织化学(S-P法)检测肺肿瘤标本(肺炎性假瘤、鳞状细胞癌、腺癌、大细胞癌、典型类癌、非典型类癌、大细胞神经内分泌癌和小细胞肺癌)及相应正常肺标本中hASH1、嗜铬粒蛋白A、突触素和CD56的表达。应用蛋白质免疫印迹法和逆转录聚合酶链反应(RT-PCR)检测肺癌组织中hASH1蛋白及mRNA的表达。
hASH1表达在典型类癌中为2/16(12.5%)、非典型类癌中为15/20(75%)、大细胞神经内分泌癌中为6/10(60%)、小细胞肺癌中为31/40(77.5%)呈阳性,而在正常肺组织(0/10)、肺炎性假瘤(0/49)、鳞状细胞癌(0/30)、腺癌(0/30)或大细胞癌(0/20)中均为阴性。典型类癌与非典型类癌的hASH1表达有显著差异(P<0.01),但大细胞神经内分泌癌与小细胞肺癌之间无差异(P>0.05)。hASH1表达与嗜铬粒蛋白A、突触素和CD56表达高度密切相关(P<0.05)。
hASH1是一种新型的肺神经内分泌肿瘤高度特异性标志物,可应用于肺神经内分泌肿瘤的临床病理诊断。