Neuroendocrine Tissue-specific Transcription Factor, BETA2/NeuroD, in Gastric Carcinomas: A Comparison with Chromogranin A and Synaptophysin Expressions

Fujii, Akiko; Kamiakito, Tomoko; Takayashiki, Norio; Fujii, Takeshi; Tanaka, Akira

doi:10.1078/0344-0338-00456

Cited by 13 publications

(20 citation statements)

References 18 publications

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“…21 It was reported that the expression of NeuroD was detected in 24.3% of gastric adenocarcinomas, but not in gastric neuroendocrine carcinomas, including small cell carcinomas. 22 The expression of NeuroD in our study was 59% in large cell neuroendocrine carcinoma and 13% in small cell carcinoma. The frequency of the expression of NeuroD was higher in large cell neuroendocrine carcinoma, but it was also observed in carcinoid tumor and classic large cell carcinoma.…”

Section: Discussionsupporting

confidence: 44%

Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: a morphological, immunohistochemical, and molecular analysis

et al. 2006

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The distinction between pulmonary large cell neuroendocrine carcinoma and small cell carcinoma is difficult in some cases. Some propose that these carcinomas should be classified as one high-grade neuroendocrine carcinoma. We examined biological features of small cell carcinoma (n ¼ 23), large cell neuroendocrine carcinoma (n ¼ 17), and classic large cell carcinoma (n ¼ 12). The average ratio of nuclear diameter of the tumor cells to that of lymphocytes for small cell carcinoma was smaller than that for large cell neuroendocrine carcinoma (Po0.0001). The frequencies of the expressions of CD56, mASH1, TTF-1, and p16 were higher and that of NeuroD was lower in small cell carcinoma than in large cell neuroendocrine carcinoma. The frequency of loss of heterozygosity at 3p was higher in high-grade neuroendocrine carcinomas than in classic large cell carcinoma (P ¼ 0.0002). Allelic losses at D5S422 (5q33) were more frequent in small cell carcinoma than in large cell neuroendocrine carcinoma (P ¼ 0.0091). Mean fractional regional loss indices of the tumors were 0.38, 0.65, and 0.72 for patients with classic large cell carcinoma, large cell neuroendocrine carcinoma, and small cell carcinoma, respectively (P ¼ 0.0003). Five-year overall survivals of patients with classic large cell carcinoma, large cell neuroendocrine carcinoma and small cell carcinoma in stage I were 67, 73, 60%, respectively. Patients with NeuroD expression had better survivals, and those with p63 expression had poorer survivals in large cell neuroendocrine carcinoma. Patients with TTF-1 expression had poorer survivals in small cell carcinoma. Our data suggest that large cell neuroendocrine carcinoma and small cell carcinoma are different morphologically, phenotypically, and genetically, although there are some overlapping features. Although further studies are needed to analyze the biological behavior of high-grade neuroendocrine carcinomas including sensitivity to chemotherapy, the pathological distinction of large cell neuroendocrine carcinoma from small cell carcinoma may be necessary to treat the patients with neuroendocrine tumors.

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Section: Discussionsupporting

confidence: 44%

Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: a morphological, immunohistochemical, and molecular analysis

et al. 2006

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“…5 On the other hand, previous study revealed the positive expression of NeuroD in pulmonary large-cell neuroendocrine carcinoma and carcinoids but not in gastric small-cell carcinomas. 8,9 In the present study, mASH1 was highly (sensitivity of 71%) and specifically (specificity of 95%) expressed in poorly differentiated neuroendocrine carcinoma, which was in accordance with our previous study. However, positivity of mASH1 did not affect the prognosis of poorly differentiated neuroendocrine carcinoma patients.…”

Section: Discussionsupporting

confidence: 80%

“…Furthermore, poorly differentiated neuroendocrine carcinomas were subdivided into small-cell type (n ¼ 8) and large-cell type (n ¼ 6) on the basis of histological findings using the criteria commonly applied to pulmonary neuroendocrine carcinomas. 9 The histological feature of small-cell neuroendocrine carcinomas was minimal cytoplasm, a fusiform cell shape, finely granular chromatin, small or absent nucleoli, and nuclear molding. The histological feature of large-cell neuroendocrine carcinomas was more cytoplasm, a round or polygonal cell shape, prominent nucleoli, and a coarse chromatin pattern.…”

Section: Patients and Tissuesmentioning

confidence: 99%

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The expression of NeuroD and mASH1 in the gastroenteropancreatic neuroendocrine tumors

et al. 2008

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Gastroenteropancreatic neuroendocrine tumors are uncommon and their tumor biology has not been well elucidated to date. Currently the WHO classification is widely used for the diagnosis and distinction of this tumor entity, which is sometimes cumbersome. Although neuroendocrine tumor markers do exist (ie chromograninA, synaptopyhsin, etc), sensitive and specific markers that accurately predict tumor growth and tumor behavior are still absent. In the present study, we assessed the expression of transcription factors (NeuroD and mASH1) essential for the normal fetal neuronal development in 33 gastroenteropancreatic neuroendocrine tumor patients (12 well-differentiated neuroendocrine tumors, 7 well-differentiated neuroendocrine carcinomas, and 14 poorly differentiated neuroendocrine carcinomas). NeuroD was less expressed in poorly differentiated neuroendocrine carcinoma (small-cell type) compared to well-differentiated neuroendocrine tumor (carcinoid) by reverse transcription-polymerase chain reaction. Immunohistochemical staining revealed that mASH1 was highly (sensitivity of 71%) and specifically (specificity of 95%) expressed in poorly differentiated neuroendocrine carcinoma. High NeuroD expression was seen in all well-differentiated neuroendocrine carcinoma and tumor (carcinoid) patients. Low NeuroD expression was seen in 36% (5 of 14) of poorly differentiated neuroendocrine carcinoma patients, which was associated with significant shorter overall survival. The expression pattern of these transcription factors may represent the biological and pathophysiological difference of gastroenteropancreatic neuroendocrine tumors and may become a new marker for the distinction of gastroenteropancreatic neuroendocrine tumors. Keywords: NeuroD; mASH1; hASH1; gastroenteropancreatic; neuroendocrine tumor Neuroendocrine tumors are a group of tumors originating from cells of the diffuse endocrine system. The diffuse endocrine system includes a number of endocrine cells spreading throughout all the body with the ability to secrete bioactive peptides and amines. Gastroenteropancreatic neuroendocrine tumors are fairly rare, and the pathophysiology of this tumor entity has not been well documented to date. Moreover diagnosis and target treatment is limited and management is challenging because little is known about the cell biology and mechanistic regulation of these tumors.1 Gastroenteropancreatic neuroendocrine tumors are classified according to the WHO classification into welldifferentiated tumors and carcinomas or poorly differentiated carcinomas.2 The current WHO classification system uses both stage-related criteria (size and presence of metastases) and grade-related criteria (mitotic rate, perineural invasion, angioinvasion, and Ki-67 proliferative index) for classifying and predicting the outcome of gastroenteropancreatic neuroendocrine tumors. As this approach includes the majority of well-accepted pathologic

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“…Lee et al [64] have reported that ectopic expression of NeuroD1 in Xenopus embryos causes conversion of skin precursor epithelial cells into neurons. Recent findings show that NeuroD1 is a neuronal differentiation factor [66] , involved in gut endocrine differentiation [67][68][69] and able to interact with Rb to activate pro-opiomelanocortin expressing cells [70] .…”

Section: Transcription Factorsmentioning

confidence: 99%

Neuroendocrine Differentiation in Prostate Cancer: From Lab to Bedside

et al. 2007

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Objectives: To discuss the current knowledge on induction, production, sustenance and promotion of neuroendocrine differentiation in human prostate cancer. Methods: Review of the literature using PubMed search and scientific journal publications. Results: Morphological evidence explains some functional relationship between neuroendocrine and neoplastic surrounding cells. Transdifferentiation phenomenon and new biochemical pathways could be included in the development of androgen independence and prostate cancer progression. Conclusion: Multiple evidence seems to confirm that a synergistic functional network between epithelial PSA secretory cells and neuroendocrine intraprostatic system is the main trigger for the induction and sustenance of neuroendocrine differentiation. The development of new antineoplastic molecules should consider the multiple interference of the intercellular network.

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Neuroendocrine Tissue-specific Transcription Factor, BETA2/NeuroD, in Gastric Carcinomas: A Comparison with Chromogranin A and Synaptophysin Expressions

Cited by 13 publications

References 18 publications

Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: a morphological, immunohistochemical, and molecular analysis

Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: a morphological, immunohistochemical, and molecular analysis

The expression of NeuroD and mASH1 in the gastroenteropancreatic neuroendocrine tumors

Neuroendocrine Differentiation in Prostate Cancer: From Lab to Bedside

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