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

研究成果: Article

84 引用 (Scopus)

抄録

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).

元の言語English
ページ(範囲)222-229
ページ数8
ジャーナルModern Pathology
17
発行部数2
DOI
出版物ステータスPublished - 2004 2
外部発表Yes

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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

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

これを引用

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.

:: Modern Pathology, 巻 17, 番号 2, 02.2004, p. 222-229.

研究成果: Article

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, 巻. 17, 番号 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. :: Modern Pathology. 2004 ; 巻 17, 番号 2. pp. 222-229.
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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).",
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T1 - hASH1 expression is closely correlated with endocrine phenotype and differentiation extent in pulmonary neuroendocrine tumors

AU - Jiang, Shi Xu

AU - Kameya, Toru

AU - Asamura, Hisao

AU - Umezawa, Atsuko

AU - Sato, Yuichi

AU - Shinada, Jun

AU - Kawakubo, Yasuaki

AU - Igarashi, Toru

AU - Nagai, Kanji

AU - Okayasu, Isao

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N2 - 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).

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KW - Achaete

KW - hASH1

KW - MASH1

KW - Neuroendocrine tumor

KW - Pulmonary neoplasm

KW - Scute

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