AIMS: Telomerase is reactivated in most cancers and there is accumulating evidence that this is a driver event in malignant melanoma (MM). Thus, our aim was to evaluate if in-situ hybridization (ISH)-based quantification of telomerase RNA (hTR) could be used to distinguish MM from naevi, and if there was a correlation with the Breslow thickness. RESULTS AND METHODS: We created a tissue microarray (TMA) from formalin-fixed and paraffin-embedded tissue samples from 17 MM and 23 naevi, performed ISH targeting hTR, and quantified the signals. We found a more than eightfold greater number of hTR signals per nucleus in the MM samples compared to the naevi, and a positive correlation (P = 0.0381) between the number of hTR signals per nucleus and the Breslow thickness. CONCLUSION: Quantification of hTR ISH signals clearly distinguish MM from naevi (P < 0.0001) and the number of signals per nucleus correlates with the Breslow thickness, suggesting that hTR might be a valuable biomarker in MM. Furthermore, as ISH-based detection requires the presence of both hTR and telomerase reverse transcriptase (hTERT), it might be an indicator of active telomerase and thus have future relevance as a predictive biomarker for anti-telomerase treatment.
AIMS: Telomerase is reactivated in most cancers and there is accumulating evidence that this is a driver event in malignant melanoma (MM). Thus, our aim was to evaluate if in-situ hybridization (ISH)-based quantification of telomerase RNA (hTR) could be used to distinguish MM from naevi, and if there was a correlation with the Breslow thickness. RESULTS AND METHODS: We created a tissue microarray (TMA) from formalin-fixed and paraffin-embedded tissue samples from 17 MM and 23 naevi, performed ISH targeting hTR, and quantified the signals. We found a more than eightfold greater number of hTR signals per nucleus in the MM samples compared to the naevi, and a positive correlation (P = 0.0381) between the number of hTR signals per nucleus and the Breslow thickness. CONCLUSION: Quantification of hTR ISH signals clearly distinguish MM from naevi (P < 0.0001) and the number of signals per nucleus correlates with the Breslow thickness, suggesting that hTR might be a valuable biomarker in MM. Furthermore, as ISH-based detection requires the presence of both hTR and telomerase reverse transcriptase (hTERT), it might be an indicator of active telomerase and thus have future relevance as a predictive biomarker for anti-telomerase treatment.
Authors: Javier A Baena-Del Valle; Qizhi Zheng; David M Esopi; Michael Rubenstein; Gretchen K Hubbard; Maria C Moncaliano; Andrew Hruszkewycz; Ajay Vaghasia; Srinivasan Yegnasubramanian; Sarah J Wheelan; Alan K Meeker; Christopher M Heaphy; Mindy K Graham; Angelo M De Marzo Journal: J Pathol Date: 2017-11-14 Impact factor: 7.996