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

Shi Xu Jiang, Toru Kameya, Hisao Asamura, Atsuko Umezawa, Yuichi Sato, Jun Shinada, Yasuaki Kawakubo, Toru Igarashi, Kanji Nagai, Isao Okayasu

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

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 < 0.0001, r = 0.852), but was not related to neural cell adhesion molecule expression (P = 0.8892), suggesting that hASH1 expression, at least in lung cancer, is associated with endocrine phenotype expression other than 'neuroendocrine differentiation' in a broad sense. The fact that hASH1 was virtually absent in almost fully differentiated typical carcinoids, but was expressed in most, if not all, less differentiated atypical carcinoids as well as large-cell neuroendocrine carcinomas and small-cell carcinomas, suggests that hASH1 expression in lung cancer imitates its early and transient expression in fetal development, and that hASH1 is instrumental in the establishment, but not in the maintenance, of a cellular endocrine phenotype. Finally, hASH1 expression correlated with a significantly shortened survival in small-cell carcinoma patients (P = 0.041).

Original languageEnglish
Pages (from-to)222-229
Number of pages8
JournalModern Pathology
Volume17
Issue number2
DOIs
Publication statusPublished - 2004 Feb
Externally publishedYes

Fingerprint

Large Cell Carcinoma
Small Cell Carcinoma
Neuroendocrine Tumors
Carcinoid Tumor
Neuroendocrine Carcinoma
Gastrin-Releasing Peptide
Phenotype
Neural Cell Adhesion Molecules
Chromogranin A
Lung Neoplasms
Neuroendocrine Cells
Lung
Calcitonin
Adenocarcinoma
Fetal Development
Tumor Cell Line
Drosophila
In Situ Hybridization
Squamous Cell Carcinoma
Maintenance

Keywords

  • Achaete
  • hASH1
  • MASH1
  • Neuroendocrine tumor
  • Pulmonary neoplasm
  • Scute

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

hASH1 expression is closely correlated with endocrine phenotype and differentiation extent in pulmonary neuroendocrine tumors. / Jiang, Shi Xu; Kameya, Toru; Asamura, Hisao; Umezawa, Atsuko; Sato, Yuichi; Shinada, Jun; Kawakubo, Yasuaki; Igarashi, Toru; Nagai, Kanji; Okayasu, Isao.

In: Modern Pathology, Vol. 17, No. 2, 02.2004, p. 222-229.

Research output: Contribution to journalArticle

Jiang, SX, Kameya, T, Asamura, H, Umezawa, A, Sato, Y, Shinada, J, Kawakubo, Y, Igarashi, T, Nagai, K & Okayasu, I 2004, 'hASH1 expression is closely correlated with endocrine phenotype and differentiation extent in pulmonary neuroendocrine tumors', Modern Pathology, vol. 17, no. 2, pp. 222-229. https://doi.org/10.1038/modpathol.3800038
Jiang, Shi Xu ; Kameya, Toru ; Asamura, Hisao ; Umezawa, Atsuko ; Sato, Yuichi ; Shinada, Jun ; Kawakubo, Yasuaki ; Igarashi, Toru ; Nagai, Kanji ; Okayasu, Isao. / hASH1 expression is closely correlated with endocrine phenotype and differentiation extent in pulmonary neuroendocrine tumors. In: Modern Pathology. 2004 ; Vol. 17, No. 2. pp. 222-229.
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