Telomerase reverse transcriptase immunohistochemical expression is sensitive but not specific for TERT gene amplification in acral melanoma

Author:

Cho Woo Cheal1ORCID,Li Wen23,Gu Jun4,Wang Wei‐Lien15,Ning Jing6,Sfamenos Steven4,Gill Pavandeep7ORCID,Nagarajan Priyadharsini1ORCID,Curry Jonathan L.158ORCID,Lazar Alexander J.1589,Prieto Victor G.18ORCID,Torres‐Cabala Carlos A.18ORCID,Aung Phyu P.1ORCID

Affiliation:

1. Department of Pathology The University of Texas MD Anderson Cancer Center Houston Texas USA

2. Division of Clinical and Translational Sciences, Department of Internal Medicine The University of Texas McGovern Medical School at Houston Houston Texas USA

3. 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

4. Cytogenetics Training Laboratory, School of Health Professions The University of Texas MD Anderson Cancer Center Houston Texas USA

5. Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer Center Houston Texas USA

6. Department of Biostatistics The University of Texas MD Anderson Cancer Center Houston Texas USA

7. Department of Pathology Royal Jubilee Hospital Victoria British Columbia Canada

8. Department of Dermatology The University of Texas MD Anderson Cancer Center Houston Texas USA

9. Department of Genomic Medicine The University of Texas MD Anderson Cancer Center Houston Texas USA

Abstract

AbstractBackgroundTERT 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.MethodsAMs (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.ResultsTERT 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.ConclusionsThe clinical utility of TERT IHC to predict TGA status in AMs appears to be limited given its low specificity and positive predictive value.

Funder

Melanoma Research Alliance

National Cancer Institute

Publisher

Wiley

Subject

Dermatology,Histology,Pathology and Forensic Medicine

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