ETS1, nucleolar and non-nucleolar TERT expression in nevus to melanoma progression
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Jaskaren S. Kohli1,6, Hira Mir2,7, Afsheen Wasif2,7, Heung Chong1,2, Victoria Akhras1,3, Rajiv Kumar4, Eduardo Nagore5 and Dorothy C. Bennett1
1Molecular and Clinical Sciences Research Institute, St George’s, University of London, London, UK
2Department of Cellular Pathology, St George’s University Hospitals NHS Foundation Trust, London, UK
3Department of Dermatology, St George’s University Hospitals NHS Foundation Trust, London, UK
4Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany
5Department of Dermatology, Instituto Valenciano de Oncología, Valencia, Spain
6Current/Present address: European Research Institute for The Biology of Aging, University Medical Center Groningen, Groningen, The Netherlands
7Current/Present address: King’s College Hospital Foundation Trust, London, UK
Dorothy C. Bennett, email: [email protected]
Keywords: TERT; ETS1; melanoma; nevus; nucleolus
Received: July 20, 2017 Accepted: October 03, 2017 Published: November 01, 2017
TERT (telomerase reverse transcriptase) is the catalytic component of telomerase. TERT shows little expression in normal somatic cells but is commonly re-expressed in cancers, facilitating immortalization. Recently-discovered TERT promoter mutations create binding sites for ETS-family transcription factors to upregulate TERT. ETS1 is reported to be important for TERT upregulation in melanoma. However it is unclear when in melanoma progression TERT and ETS1 proteins are expressed. To elucidate this question, ETS1 and TERT immunohistochemistry were performed on a panel of benign (n=27) and dysplastic nevi (n=34), radial growth phase (n=29), vertical growth phase (n=25) and metastatic melanomas (n=27). Lesions were scored by percentage of positive cells. ETS1 was readily detectable in all lesions, but not in normal melanocytes. TERT was located in either the nucleolus, the nucleoplasm (non-nucleolar) or both. Non-nucleolar TERT increased in prevalence with progression, from 19% of benign nevi to 78% of metastases. It did not however correlate with cell proliferation (Ki-67 immunostaining), nor differ significantly in prevalence between primary melanomas with or without a TERT promoter mutation. These results demonstrate that ETS1 is expressed very early in melanoma progression, and interestingly only non-nucleolar TERT correlates clearly in prevalence with melanoma progression. It can be acquired at various stages and by mechanisms other than promoter mutations.
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