Enhancer of Zeste Homolog 2 (EZH2) in Malignant Progression of Gallbladder Carcinoma
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ORIGINAL RESEARCH
Enhancer of Zeste Homolog 2 (EZH2) in Malignant Progression of Gallbladder Carcinoma Gayatri Behera 1 & Suvradeep Mitra 1 & Tushar S Mishra 2 & Suvendu Purkait 1 Accepted: 6 October 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose Data related to the role of epigenetic modifications in gallbladder carcinoma (GBC) is limited. We intended to assess the role of crucial epigenetic modifiers pertaining to histone modification and DNA-methylation system in gallbladder carcinogenesis. Methods The expression of EZH2, H3K27me3, and DNA methyltransferases (DNMTs) was analyzed by immunohistochemistry in cases of GBC (n = 39), gallbladder dysplasia (GBD, n = 12), and benign mucosa (BM, n = 16). A semi-quantitative scoring system was used for assessing the immunohistochemical expression. Results The expression of EZH2 was significantly higher in cases of GBC than GBD (p value 0.001). The cases of BM were negative. Its expression was also higher in poorly differentiated tumors and positively correlated with the proliferative activity (MIB-1 labeling index) (p value 0.03 and 0.01, respectively). There was no significant difference in the expression levels of H3K27me3, DNMT-1, and DNMT-3B among GBC, GBD, and BM cases. Although GBC cases with strong EZH2 expression showed a shorter overall survival, the difference was not statistically significant. Conclusion This study highlights the crucial role of the key epigenetic regulators EZH2 in the pathobiology and evolution of gallbladder carcinogenesis. Given the reversibility of epigenetic alterations, EZH2 may be a novel therapeutic target for gallbladder carcinogenesis. Keywords Gallbladder . Carcinoma . Dysplasia . Epigenetic . EZH2 . H3K27me3 . DNMT
Introduction Gallbladder carcinoma (GBC) is one of the most aggressive malignant tumors of the gastrointestinal tract [1]. The majority Gayatri Behera and Suvradeep Mitra contributed equally to this work. Gayatri Behera and Suvradeep Mitra share the first authorship. * Suvendu Purkait [email protected] Gayatri Behera [email protected] Suvradeep Mitra [email protected] Tushar S Mishra [email protected] 1
Department of Pathology and Lab Medicine, AIIMS, Bhubaneswar 751019, India
2
Department of Trauma and Emergency, AIIMS, Bhubaneswar 751019, India
of the cases are diagnosed at an advanced stage, conferring a dismal prognosis due to rapid progression and lack of specific treatment modality. The overall survival period for GBC is less than a year with a 5-year cancer-specific survival rate of only 26%, even after surgical resection [1, 2]. The key molecular events associated with the transition from normal to preinvasive to invasive malignancy (GBC) are not well established. Hence, an insight into the precise molecular mechanisms of GBC progression is the need of the hour to produce newer diagnostic markers and novel therapeutic targets. The study of epigenetic alterations, namely DNA methylation and histone modifications, is crucial in cancer research in r
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