In-situ hybridization-based quantification of hTR: a possible biomarker in malignant melanoma

Histopathology. 2015 Apr;66(5):747-51. doi: 10.1111/his.12501. Epub 2015 Jan 20.

Abstract

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.

Keywords: biomarker; hTERC; hTERT; hTR; in-situ hybridization; melanoma; rolling circle amplification; telomerase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization / methods
  • Melanoma / diagnosis
  • Melanoma / enzymology*
  • Nevus / diagnosis
  • Nevus / enzymology*
  • RNA / metabolism*
  • Skin Neoplasms / diagnosis
  • Skin Neoplasms / enzymology*
  • Telomerase / metabolism*

Substances

  • Biomarkers, Tumor
  • telomerase RNA
  • RNA
  • Telomerase