Neuroendocrine tissue-specific transcription factor, BETA2/NeuroD, in gastric carcinomas: a comparison with chromogranin A and synaptophysin expressions.

BETA2/NeuroD (NeuroD) is a basic helix-loop-helix type of transcription factor mainly involved in neuroendocrine differentiation. In this study, we evaluated the prevalence of neuroendocrine differentiation in gastric carcinomas by analyzing the NeuroD expression in comparison with those of chromogranin A and synaptophysin. Of the 70 cases of gastric adenocarcinoma, the expressions of NeuroD, chromogranin A, and synaptophysin were detected in 17 (24.3%), four (5.7%), and 24 cases (34.3%), respectively, with preferential expressions in a non-solid type of poorly differentiated adenocarcinoma. The expression pattern of NeuroD was mostly concordant with that of synaptophysin and partly with chromogranin A, indicating that NeuroD serves as a good neuroendocrine marker in gastric adenocarcinomas. On the other hand, no immunoreactivity against NeuroD was detectable in nine cases of gastric neuroendocrine carcinomas, including small cell carcinomas, despite the presence of synaptophysin and chromogranin A expressions. These findings led us to conclude that neuroendocrine differentiation is estimated to be present in 20-30% of gastric adenocarcinomas with preference to a non-solid type of poorly differentiated adenocarcinoma. In addition, the negative expression of NeuroD in neuroendocrine carcinomas suggests that other regulatory mechanisms are possibly involved in the development of neuroendocrine carcinoma.