1. ¹Department of General Surgery, Chiba University Graduate School of Medicine, Chiba, Japan
2. ²Department of Molecular Pathology, Chiba University Graduate School of Medicine, Chiba, Japan
3. ³Department of Pathology, Jikei University School of Medicine, Tokyo, Japan
4. ⁴Department of Surgery, Teikyo University, Chiba, Japan
5. ⁵Department of Surgery, Chiba Aoba Hospital, Chiba, Japan
6. ⁶Department of Diagnostic Pathology, Chiba University Graduate School of Medicine, Chiba, Japan

Correspondence: Dr T Shida, MD, PhD, Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan. E-mail: shidax812@yahoo.co.jp

Received 24 April 2008; Revised 27 May 2008; Accepted 28 May 2008; Published online 27 June 2008.

Abstract

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.