TELOMERASE CATALYTIC SUBUNIT mRNA IN LARYNGEAL SQUAMOUS CELL CARCINOMAS

Background. Re-activation of the enzyme telomerase, has been detected in nearly 90% of human malignancies. In contrast, normal human somatic cells, with the exception of germ cells and stem cells of renewable tissues, do not have detectable telomerase activity. Transcription of human telomerase catalytic subunit (hTERT) gene represents a ratelimiting step for telomerase activity, a key enzyme implicated in cellular immortalisation and transformation. The aim of our study was to explore the hypothesis that quantitative differences exist in the level of hTERT mRNA expression between laryngeal squamous cell carcinomas (LC) and the surrounding normal or reactive hyperplastic laryngeal mucosa, in order to obtain insights into the role of telomerase re-activation in the multistep process of laryngeal carcinogenesis. Methods. We tested 45 LC and 45 normal or reactive hyperplastic laryngeal epithelia (control tissue) from the same patients for the presence of human telomerase catalytic subunit (hTERT) mRNA by using Roche LightCycler Telo TAGGG hTERT Quantification kit. The hTERT index was calculated to express the relative quantity levels of hTERT mRNA. Results. hTERT mRNA was detectable in 12 of 45 (27%) control laryngeal epithelia and 37 of 45 LC (82%); 3 of 5 grade 1 (60%), 14 of 19 grade 2 (74%) and 20 of 21 grade 3 (95%) LC. The mean hTERT indices were 0.10 for control laryngeal tissue, 0.68 for grade I, 2.16 for grade II and 2.56 for grade III LC. The differences between hTERT indices in the control laryngeal epithelia and LC are statistically significant (p < 0.05). Although progressive increase of mean hTERT indices was observed with increasing histological grade of LC, the differences did not reach statistical significance. Conclusions. We believe that low relative quantities of hTERT mRNA found occasionally in normal and reactive hyperplastic laryngeal epithelium originate from the stem cells and correspond to a self-renewal capacity of the squamous epithelium. However, higher relative quantities of hTERT mRNA in the majority of LC are the consequence of telomerase reactivation in the multistep process of laryngeal carcinogenesis, reflecting the appearance of immortal cell population(s).