hASH1 expression is closely correlated with endocrine phenotype and differentiation extent in pulmonary neuroendocrine tumors

• Published in: Modern pathology 2004-02, Vol.17 (2), p.222-229
• Main Authors: Jiang, Shi-Xu, Kameya, Toru, Asamura, Hisao, Umezawa, Atsuko, Sato, Yuichi, Shinada, Jun, Kawakubo, Yasuaki, Igarashi, Toru, Nagai, Kanji, Okayasu, Isao
• Format: Article
• Language: English
• Subjects: achaete; Adenocarcinoma - metabolism; Adenocarcinoma - mortality; Adenocarcinoma - pathology; Basic Helix-Loop-Helix Transcription Factors; Biomarkers, Tumor - analysis; Carcinoid Tumor - metabolism; Carcinoid Tumor - mortality; Carcinoid Tumor - pathology; Carcinoma, Neuroendocrine - metabolism; Carcinoma, Neuroendocrine - mortality; Carcinoma, Neuroendocrine - pathology; Carcinoma, Small Cell - metabolism; Carcinoma, Small Cell - mortality; Carcinoma, Small Cell - pathology; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - mortality; Carcinoma, Squamous Cell - pathology; DNA-Binding Proteins - biosynthesis; hASH1; Humans; Immunohistochemistry; Laboratory Medicine; Lung Neoplasms - metabolism; Lung Neoplasms - mortality; Lung Neoplasms - pathology; MASH1; Medicine; Medicine & Public Health; neuroendocrine tumor; original-article; Pathology; Phenotype; pulmonary neoplasm; RNA, Messenger - analysis; scute; Survival Analysis; Transcription Factors - biosynthesis
• ISSN: 0893-3952; 1530-0285
• DOI: 10.1038/modpathol.3800038

The human homolog 1 of the Drosophila neurogenic achaete–scute genes, hASH1, is specifically expressed in fetal pulmonary neuroendocrine cells and in some neuroendocrine tumor cell lines. However, no data have been gathered regarding its in vivo expression in tumors. hASH1 mRNA expression was investigated by in situ hybridization in 238 surgically resected lung carcinomas, and the correlations between hASH1 expression status and immunostaining results of neuroendocrine markers chromogranin A, neural cell adhesion molecule, gastrin-releasing peptide and calcitonin, and clinical outcome were analyzed. hASH1 expression was detected in 2/20 (10%) adenocarcinomas, 4/30 (13.3%) typical carcinoids, 11/13 (84.6%) atypical carcinoids, 38/67 (56.7%) large-cell neuroendocrine carcinomas and 56/78 (71.8%) small-cell carcinomas, respectively, but not in any squamous cell carcinoma (0/21) or large-cell carcinoma (0/9). The 2 hASH1+ adenocarcinomas also expressed multiple neuroendocrine markers. Thus, hASH1 expression was restricted to lung cancers with neuroendocrine phenotypes. However, not all neuroendocrine tumors expressed hASH1. Within the entities of large-cell neuroendocrine carcinoma and small-cell carcinoma, hASH1 expression correlated very closely with chromogranin A, gastrin-releasing peptide and calcitonin expression (P