Abstract 1761: Class I HDAC expression patterns in gastroenteropancreatic neuroendocrine tumors

Abstract

Abstract Aims Inhibition of histone deacetylases (HDACs) has been shown to have antiproliferative and proapoptotic effects on gastrointestinal neuroendocrine tumor cells in vitro. While several HDAC inhibitors have entered clinical trials as antineoplastic agents in various tumor entities, information on the expression of HDACs in gastroenteropancreatic neuroendocrine tumors (GEP-NET) in vivo is still lacking. Methods We investigated expression of class I HDAC1, HDAC2 and HDAC3 in a large cohort of neuroendocrine tumors by immunohistochemistry and correlated our findings with clinicopathologic variables, proliferative activity and patient prognosis. Results While 58 (59.2%) out of 98 neuroendocrine foregut and midgut tumors did not display any nuclear expression of HDAC1, HDAC2 or HDAC3, 38 (38.8%) were partially positive, i.e. showed nuclear staining for at least one of the three HDAC isoforms. Only 2 (2.0%) tumors were positive for all of the three HDACs. Nuclear expression of HDAC isoforms correlated strongly (p<0.006) with each other and also correlated with proliferative capacity as determined by expression of Ki67 (p=0.003). Consequently, expression of HDAC1 in foregut tumors was correlated with grading (p=0.009) and a similar tendency was seen for HDAC2 (p=0.077). No correlation was seen between HDAC expression in primary tumors and tumor stage, nodal status or state of metastasis. However, HDAC expression was lower in nodal foregut and midgut lesions when compared to the corresponding primary tumors (p<0.023). HDAC expression was not associated with disease specific survival in stage IV midgut tumors. Conclusion Our observation of a tight association of HDAC positivity and proliferative activity in GEP-NETs mirror the fact that overexpression of HDACs promote cancer cell growth in these neoplasms in vivo. We additionaly hypothesize that differences in HDAC expression might predict response to HDAC inhibitors which should be taken into account when future clinical trials with these substances are being planned. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1761.