EZH2 Expression in Invasive Squamous Cell Carcinoma of the Lung and Its Precursor Lesions.
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 reported to be expressed in multiple malignant neoplasms, but with only limited studies in squamous cell carcinoma (SCC) of the lung and no published reports of EZH2 expression in squamous precursor lesions. The aim of this study was to examine EZH2 expression in invasive SCC of the lung and its precursor lesions, including mild, moderate, and severe dysplasia and carcinoma in situ (CIS).
Design: Tissue microarrays constructed from 99 invasive SCC cases were immunohistochemically studies using a monoclonal antibody against EZH2 (Leica). A separate cohort of 17 resected lung SCC cases with squamous precursor lesions was immunohistochemically studied for EZH2 expression. 2004 WHO definitions of squamous precursor lesions were utilized. Nuclear staining for EZH2 was considered positive. The percentage of positively stained cells was recorded and the staining intensity was graded as negative, weak, moderate or strong. A p value of <0.05, determined by Fisher's exact test, was considered statistically significant.
Results: Ninety (90.9%) of 99 cases of invasive SCC were immunohistochemically positive for EZH2. Normal respiratory epithelium generally included scattered weakly to moderately EZH2 positive cells in the basal layer, with only 2 (11.1%) of 17 cases demonstrating moderate to strong staining in a majority of bronchiolar epithelial cells. In contrast, nearly all areas of squamous metaplasia, dysplasia and CIS were moderately to strongly positive for EZH2 in the majority of cells, with 4 (80%) of 5 cases of squamous metaplasia, 10 (90.9%) of 11 cases of mild dysplasia, 12 (100%) of 12 cases of moderate dysplasia, and all 5 (100%) of 5 cases of severe dysplasia demonstrating moderate to strong EZH2 positivity. Interestingly, only 9 (69.2%) of 13 cases of CIS and 13 (76.5%) of 17 cases of invasive SCC were moderately to strongly EZH2 positive. The frequency of EZH2 expression was significantly different (p<0.0001) between bronchiolar epithelial cells and squamous metaplasia, dysplasia, CIS or invasive SCC.
Conclusions: Our studies showed that EZH2 expression is present in a high proportion of SCC of the lung, as well as its squamous precursor lesions, including squamous metaplasia, squamous dysplasia and CIS, as compared with only limited expression in normal bronchiolar epithelium. These findings indicate that EZH2 expression may be involved in the early stages of carcinogenesis.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 251, Tuesday Afternoon