[Expression and clinicopathologic significance of human achaete-scute homolog 1 in pulmonary neuroendocrine tumors].
OBJECTIVE
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Li
Fei
F
Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang 110001, China.
Zhong
Zhiyong
Z
Li
Rui
R
Huang
Heyu
H
Wang
Lijun
L
Zheng
Donghan
D
Zhang
Daorong
D
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018278:Carcinoma, Neuroendocrine / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D018358:Neuroendocrine Tumors / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055752:Small Cell Lung Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology
D051792:Basic Helix-Loop-Helix Proteins; C065500:ASCL1 protein, human