Epigenetic markers in basal cell carcinoma: universal themes in oncogenesis and tumor stratification? - a short report

Springer Science and Business Media LLC - Tập 41 - Trang 693-698 - 2018
Rajesh C. Rao1,2,3,4, May P. Chan2,5, Chris A. Andrews1, Alon Kahana1,3
1Department of Ophthalmology and Visual Sciences, W. K. Kellogg Eye Center, University of Michigan, Ann Arbor, USA
2Department of Pathology, University of Michigan, Ann Arbor, USA
3Comprehensive Cancer Center, University of Michigan, Ann Arbor, USA
4Section of Ophthalmology, Surgery Service, VA Ann Arbor Health System, Ann Arbor, USA
5Department of Dermatology, University of Michigan, Ann Arbor, USA

Tóm tắt

Advanced basal cell carcinomas (BCCs) suffer from a scarcity of effective treatment options. Previously, we found that the targetable histone methyltransferase EZH2 was upregulated in aggressive BCC subtypes, suggesting that epigenetics may play a role in BCC progression. The purpose of this study was to determine whether EZH2-associated proteins and marks may be employed for the stratification of BCC histologic subtypes. Sixty-two specimens (from 61 patients), representing more or less aggressive BCC histologic subtypes and matching non-malignant epidermal cells, were included in this study. Immunohistochemistry of H3K27me3, 5hmC, NSD2, MOF and JARID1B was performed to assess their putative associations with BCC histologic subtypes, as well as with EZH2 and Ki67 expression levels. We found that H3K27me3 and 5hmC upregulation was positively correlated with the occurrence of a less aggressive BCC histology. The modifications were also positively correlated with each other. Interestingly, we found that they were negatively correlated with the expression of EZH2, a marker for an aggressive BCC histology. The levels of NSD2, MOF, H3K27me3 and 5hmC were found to be universally upregulated in BCCs versus non-malignant epidermal cells. Our data reveal an EZH2-associated epigenetic marker profile that correlates with histologic signs of BCC aggressiveness. Our findings may have diagnostic and therapeutic implications, and indicate that epigenetic markers may be shared even with relatively less aggressive tumor types, thereby suggesting universal themes.

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Springer Science and Business Media LLC

Tập 41

693-698

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