EZH2 is a polycomb group protein that is involved in the progression of multiple human cancers including prostatic, endometrial, and colonic adenocarcinomas. Its expression has been shown to increase from typical carcinoid to atypical carcinoid and further to small cell/large cell neuroendocrine carcinomas of the lung. Here we examine the EZH2 expression and the proliferation index (PI) by Ki-67 expression in neuroendocrine tumors of the gastrointestinal tract (GI) and pancreas.

We retrieved 72 cases of GI and pancreatic neuroendocrine tumors of grades G1 (n = 56), G2 (n = 6) and G3 (n = 10) which were graded according to the WHO classification. Expression of EZH2 and Ki-67 was analyzed by immunohistochemistry using monoclonal antibodies (EZH2 at 1:200; Ki-67 at 1:70). Expression of EZH2 was determined to be low (10%), and was compared with the respective PI.

All G1 tumors had low EZH2 expression and a low PI (20%). In G2 tumors, EZH2 expression was intermediate (1-10%) and PI was between 0-8%. One of the G2 tumors had a low PI of 0, however, the EZH2 expression was intermediate (3%). There was increased EZH2 expression relative to increasing tumor grade from G1 to G3 (p <0.05).

EZH2 expression increases incrementally from G1 neuroendocrine tumors to G2 and further to G3 tumors, suggesting an association or a role in progression of neuroendocrine tumors. There is strong correlation between the expression of EZH2 and PI in G1, G2 and G3 tumors. EZH2 appears to be a better predictor of tumor grade in G2 tumors as compared to PI. Thus, EZH2 could be used as an additional diagnostic marker in examining atypical GI neuroendocrine tumors.

Citation Format: Jia Qin, Raag Agrawal, Miguel G. Echevarria, LAura A. Martello, M.A Haseeb, Raavi Gupta. Enhancer of zeste homolog 2 (EZH2) expression and proliferation index (Ki-67) in neuroendocrine tumors of the gastrointestinal tract and pancreas. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3406. doi:10.1158/1538-7445.AM2015-3406