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Enhancer of Zeste Homolog 2 (EZH2) in Malignant Progression of Gallbladder Carcinoma

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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.

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Acknowledgments

The authors are thankful to all the technical staff specially Mr. S Raheman for the technical supports.

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Author notes

  1. Gayatri Behera and Suvradeep Mitra contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology and Lab Medicine, AIIMS, Bhubaneswar, 751019, India

    Gayatri Behera, Suvradeep Mitra & Suvendu Purkait

  2. Department of Trauma and Emergency, AIIMS, Bhubaneswar, 751019, India

    Tushar S Mishra

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  1. Gayatri Behera
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  2. Suvradeep Mitra
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  3. Tushar S Mishra
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  4. Suvendu Purkait
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Correspondence to Suvendu Purkait.

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Gayatri Behera and Suvradeep Mitra share the first authorship.

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Behera, G., Mitra, S., Mishra, T.S. et al. Enhancer of Zeste Homolog 2 (EZH2) in Malignant Progression of Gallbladder Carcinoma. J Gastrointest Canc 52, 1029–1034 (2021). https://doi.org/10.1007/s12029-020-00536-3

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  • DOI: https://doi.org/10.1007/s12029-020-00536-3

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