PMID- 37400233 OWN - NLM STAT- MEDLINE DCOM- 20230814 LR - 20231213 IS - 1600-0560 (Electronic) IS - 0303-6987 (Linking) VI - 50 IP - 9 DP - 2023 Sep TI - Telomerase reverse transcriptase immunohistochemical expression is sensitive but not specific for TERT gene amplification in acral melanoma. PG - 845-851 LID - 10.1111/cup.14494 [doi] AB - BACKGROUND: TERT gene amplification (TGA) is a mechanism of telomerase reverse transcriptase (TERT) upregulation frequently utilized by acral melanomas (AMs). Currently, the utility of TERT immunohistochemistry (IHC) to predict TGA status in AMs is poorly documented. METHODS: AMs (26 primary and 3 metastatic) and non-acral cutaneous melanomas (6 primary) were subjected to immunohistochemical analysis using anti-TERT antibody to demonstrate protein expression and fluorescence in situ hybridization (FISH) to assess genomic copy number alteration. The relationship between TERT immunoreactivity and TGA confirmed by FISH was assessed using logistic regression. RESULTS: TERT expression was seen in 50% (13/26) of primary and 100% (3/3) of metastatic AMs and 50% (3/6) of primary non-acral cutaneous melanomas. TGA was found in 15% (4/26) and 67% (2/3) of primary and metastatic AMs and 17% (1/6) of non-acral cutaneous melanomas. The intensity of TERT immunoreactivity correlated with TGA (p = 0.04) and a higher TERT copy number-to-control ratio in AMs, with a correlation coefficient of 0.41 (p = 0.03). The sensitivity and specificity of TERT immunoreactivity for predicting TGA in AMs were 100% and 57%, with corresponding positive and negative predictive values of 38% and 100%, respectively. CONCLUSIONS: The clinical utility of TERT IHC to predict TGA status in AMs appears to be limited given its low specificity and positive predictive value. CI - (c) 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Cho, Woo Cheal AU - Cho WC AUID- ORCID: 0000-0001-5867-1403 AD - Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. FAU - Li, Wen AU - Li W AD - Division of Clinical and Translational Sciences, Department of Internal Medicine, The University of Texas McGovern Medical School at Houston, Houston, Texas, USA. AD - Biostatistics/Epidemiology/Research Design (BERD) Component, Center for Clinical and Translational Sciences (CCTS), The University of Texas Health Science Center at Houston, Houston, Texas, USA. FAU - Gu, Jun AU - Gu J AD - Cytogenetics Training Laboratory, School of Health Professions, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. FAU - Wang, Wei-Lien AU - Wang WL AD - Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. AD - Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. FAU - Ning, Jing AU - Ning J AD - Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. FAU - Sfamenos, Steven AU - Sfamenos S AD - Cytogenetics Training Laboratory, School of Health Professions, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. FAU - Gill, Pavandeep AU - Gill P AUID- ORCID: 0000-0003-4576-0049 AD - Department of Pathology, Royal Jubilee Hospital, Victoria, British Columbia, Canada. FAU - Nagarajan, Priyadharsini AU - Nagarajan P AUID- ORCID: 0000-0002-5346-2669 AD - Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. FAU - Curry, Jonathan L AU - Curry JL AUID- ORCID: 0000-0003-0630-6222 AD - Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. AD - Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. AD - Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. FAU - Lazar, Alexander J AU - Lazar AJ AD - Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. AD - Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. AD - Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. AD - Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. FAU - Prieto, Victor G AU - Prieto VG AUID- ORCID: 0000-0001-9204-7161 AD - Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. AD - Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. FAU - Torres-Cabala, Carlos A AU - Torres-Cabala CA AUID- ORCID: 0000-0001-7422-0661 AD - Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. AD - Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. FAU - Aung, Phyu P AU - Aung PP AUID- ORCID: 0000-0002-3398-0573 AD - Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. LA - eng GR - CA/NCI NIH HHS/United States GR - MRA/Melanoma Research Alliance/United States GR - CA/NCI NIH HHS/United States PT - Journal Article DEP - 20230703 PL - United States TA - J Cutan Pathol JT - Journal of cutaneous pathology JID - 0425124 RN - EC 2.7.7.49 (Telomerase) SB - IM MH - Humans MH - Gene Amplification MH - In Situ Hybridization, Fluorescence MH - *Telomerase/genetics/metabolism MH - Mutation MH - *Skin Neoplasms/diagnosis/genetics/metabolism MH - *Melanoma/diagnosis/genetics/metabolism MH - Melanoma, Cutaneous Malignant OTO - NOTNLM OT - TERT gene amplification OT - acral melanoma OT - fluorescence in situ hybridization OT - immunohistochemistry OT - telomerase reverse transcriptase EDAT- 2023/07/04 01:05 MHDA- 2023/08/14 06:42 CRDT- 2023/07/03 21:03 PHST- 2023/06/15 00:00 [revised] PHST- 2023/03/03 00:00 [received] PHST- 2023/06/19 00:00 [accepted] PHST- 2023/08/14 06:42 [medline] PHST- 2023/07/04 01:05 [pubmed] PHST- 2023/07/03 21:03 [entrez] AID - 10.1111/cup.14494 [doi] PST - ppublish SO - J Cutan Pathol. 2023 Sep;50(9):845-851. doi: 10.1111/cup.14494. Epub 2023 Jul 3.