hTERT, hTR and TERT promoter mutations as markers for urological cancers detection: A systematic review

The clinical relevance of telomerase subunits (human reverse transcriptase - hTERT, and human telomerase RNA - hTR) and TERT promotor mutations as biomarkers in genitourinary cancers was reviewed through the systematic analysis of the current literature. We performed a systematic literature search using 2 databases (Medline and Scopus) over the past 20 years. Primary outcomes were sensitivity and specificity of hTR, hTERT and TERT promoter mutations. Secondary outcomes were the biomarkers predictive values for tumor characteristics. Regarding bladder cancer, hTERT in urine showed high sensitivity (mean values: 55%-96%), and specificity (69%-100%): it correlated with bladder cancer grade and/or stage. hTR sensitivity ranged from 77% to 92%. With adapted cut-off, it demonstrated 72% to 89% specificity. TERT promoter mutation rate was up to 80% both in tissue and urine, resulting in 62%-92% sensitivity for primary tumors and 42% for relapse. Specificity ranged from 73% to 96%, no correlations with stage were observed. In prostate cancer, hTERT in tissue, prostate secretion and serum showed high sensitivity (97.9%, 36%, and 79.2%-97.5%, respectively) and specificity values (70%, 66%, 60%-100%). hTR showed very high sensitivity (88% in serum and 100% in tissue) although specificity values were highly variable depending on the series and techniques (0%-96.5%). In RCC, hTERT sensitivity on tissue ranged from 90 to 97%, specificity from 25 to 58%. There was an association of hTERT expression with tumor stage and grade. hTERT showed high accuracy in genitourinary cancers, while the value of hTR was more controversial. hTERT and TERT promotor mutations may have predictive value for bladder cancer and RCC staging and grading, while no such relationship was observed in CaP. Although telomerase subunits showed clinically relevant values in genitourinary cancers, developing fast and cost-effective methods is required before contemplating routine use.