EZH2 Expression Is Correlated with Histologic Grade of Lung Adenocarcinoma.
Jennifer J Findeis-Hosey, Loralee A McMahon, Qi Yang, Faqian Li, Haodong Xu. University of Rochester, NY
Background: Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of polycomb repressive complex 2 with histone methyltransferase activity. EZH2 has been demonstrated via immunohistochemical staining to be expressed in multiple human malignancies, including prostate carcinoma, small and large cell neuroendocrine carcinoma of the lung, and squamous cell carcinoma of the lung. The aim of this study was to examine EZH2 expression in atypical adenomatous hyperplasia (AAH), bronchioloalveolar carcinoma (BAC), and primary lung adenocarcinoma.
Design: A total of 183 cases of surgically resected lung specimens were immunohistochemically studied using a monoclonal antibody against EZH2 (Leica), including 6 cases of AAH, 7 cases of BAC, and 170 cases of primary lung adenocarcinoma. The lung adenocarcinomas were further segregated by histologic grade, and included 20 cases of well-differentiated (WD), 88 cases of moderately differentiated (MD), and 62 cases of poorly differentiated (PD) adenocarcinoma. All 170 lung adenocarcinoma cases and 2 BAC cases were examined as part of a tissue microarray, while the remaining 6 cases of AAH and 5 cases of BAC were examined as representative resection sections. The percentage of positively stained tumor cells was recorded and the staining intensity was graded as negative, weak, moderate, or strong. Nuclear staining in greater than 5% of tumor cells was considered positive for EZH2. A p value of <0.05, as determined by two-tailed Fisher's exact probability test and Chi-square test, was considered statistically significant.
Results: Immunohistochemical studies showed EZH2 staining in only 5 (25%) of 20 cases of WD adenocarcinoma, as compared with 53 (85.5%) of 62 cases of PD adenocarcinoma and 69 (78.4%) of 88 cases of MD adenocarcinoma. There was EZH2 staining in 1 (16.67%) of 6 cases of AAH, with 40% of atypical cells demonstrating moderate EZH2 positivity. There was EZH2 staining in 1 (14.29%) of 7 cases of BAC, with 10% of neoplastic cells demonstrating strong EZH2 positivity. There is a statistically significant difference in EZH2 staining among the 3 histologic grading subtypes (p<0.0001).
Conclusions: This study demonstrates that there is differential EZH2 immunohistochemical expression in preinvasive lesions (AAH and BAC) and invasive lung adenocarcinoma. Specifically, there is low frequency of EZH2 expression in AAH and BAC, and high frequency of EZH2 expression in invasive adenocarcinoma, with the majority of cases of MD and PD adenocarcinoma being positive for EZH2. These findings indicate that EZH2 expression may be associated with an aggressive biological behavior.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 250, Tuesday Afternoon