Vagner Josephine, Steiniche Torben, Stougaard Magnus
Department of Pathology, Aarhus University Hospital, Noerrebrogade 44, Building 18B, 8000, Aarhus C, Denmark.
Histopathology. 2015 Apr;66(5):747-51. doi: 10.1111/his.12501. Epub 2015 Jan 20.
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.
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.
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.
端粒酶在大多数癌症中重新激活，并且有越来越多的证据表明这是恶性黑色素瘤（MM）中的一个驱动事件。因此，我们的目的是评估基于原位杂交（ISH）的端粒酶RNA（hTR）定量是否可用于区分MM和痣，以及是否与Breslow厚度相关。
我们从17例MM和23例痣的福尔马林固定石蜡包埋组织样本中制作了组织微阵列（TMA），进行针对hTR的ISH，并对信号进行定量。我们发现MM样本中每个细胞核的hTR信号数量比痣样本多八倍以上，并且每个细胞核的hTR信号数量与Breslow厚度之间存在正相关（P = 0.0381）。
hTR ISH信号的定量可明确区分MM和痣（P < 0.0001），并且每个细胞核的信号数量与Breslow厚度相关，这表明hTR可能是MM中有价值的生物标志物。此外，由于基于ISH的检测需要同时存在hTR和端粒酶逆转录酶（hTERT），它可能是活性端粒酶的一个指标，因此作为抗端粒酶治疗的预测生物标志物可能具有未来相关性。
