Abundant Expression Of Enhancer Of Zeste Homolog 2 In Small Cell Lung Cancer

Abstract Background: Enhancer of Zeste Homolog 2 (EZH2) is a catalytic component of polycomb repressive complexes and functions as a histon methyltransferase for H3 lysine 27 residues. EZH2 overexpression promotes tumor progression and metastasis, leading to a poor prognosis. Small cell lung cancer (SCLC) is characterized by highly invasive and metastatic potentials compared with non-small cell lung cancer (NSCLC), whereas these are very limited information about whether EZH expression is associated with clinical and biological differences between both tumor types. The objective of the current study is to elucidate the role of EZH2 in the phenotypic characteristics of SCLC Method: EZH2 expressions in staging-matched tumor samples from 34 patients with SCLC and NSCLC consisting of adenocarcinoma (Ad) and squamous cell carcinoma (SCC) were evaluated using immunohistochemistry. The extent and location of immunohistochemical staining for EZH2 was assessed according to the immunoreactive score (IRS) evaluating the proportion of cells that express EZH2 protein and the intensity of its staining. Percentage of the cancer area stained in high-power fields was measured. Staining intensity was graded as 0 (negative), 1 (weak), 2 (moderate), and 3 (strong); percentage of positive cells was scored as 0 (negative), 2 (from 11 to 50%), 3 (from 51 to 80%), and 4 (> 80%). The IRS taken from the multiplication of these two scores (values from 0-12) was defined as follows: 0 as negative, values 1-3 as weak, values 4, 6 as positive, and multiplication values 8, 9, 12 as strongly positive. Results:Thirty-four patients analyzed contained, 16 (47%) of surgical stage I, 10 (29%) of Stage II, 7 (21%) of Stage III, and one (3%) of Stage IV. The patient's clinical characteristic among three groups (SCLC, Ad, and SCC group) are summarized. Sex (M/F) = (27/7, 20/14, and 31/3). Mean Age = (68.2, 65.3, and 70.4). Mean Smoking Index (the number of cigarettes per day×smoking years) = (1236, 526, and 1222). Negative staining was noted in one SCLC, five Ads, and four SCCs, weakly positive in 0 SCLC, 17 Ads, and 15 SCCs, positive in 8 SCLCs, 2 Ads, and 9 SCCs and strongly positive in 25 SCLCs, 10 Ads, and 6 SCCs. Mean IRS was 9.5 in SCLCs, 4.5 in Ads, and 3.8 in SCCs. The immunohistochemical analysis of EZH2 expression levels based on the staining intensity and the percentage of positive cells was significantly higher with SCLC (p<0.001). Conclusion:EZH2 expression may determine the clinical and biological characteristics of SCLC. Citation Format: Yasutaka Watanabe, Nobuyuki Koyama, Yuki Iwai, Chihiro Miwa, Shinichiro Koyama. Abundant expression of enhancer of zeste homolog 2 in small cell lung cancer. [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 103. doi:10.1158/1538-7445.AM2015-103