Telomerase reverse transcriptase (TERT) expression is a hallmark in
tumorigenesis and upregulated due to mutations and methylation of the human (h)TERT promoter. As mutations are rare but methylation is common in
pituitary adenomas (PA), we determined promoter methylation and its clinical impact in 85 primary and 15 recurrent PA by methylation-specific PCR. 40 females (47%) and 45 males (53%) with a median age of 53 years harboring micro-, macro-, and giant
adenomas in 12, 82, and 6% were included (
prolactinomas, corticotroph, somatotroph, gonadotroph, thyreotroph, plurihormonal, and null cell
adenomas in 11, 18, 10, 29, 1, 10, and 21%, respectively). In primary diagnosed
tumors, methylation rate was 27% and higher in males than in females (40 vs. 13%, p = 0.001) after uni- and multivariate analyses. Methylation differed among PA subtypes (0-42%, p = n.s.) and was not significantly correlated with
tumor size, cavernous sinus invasion, or serum
hormone levels. Ki67 labeling index and recurrence (N = 16, 19%) were independent of methylation. In recurrent
tumors, methylation was similar to primary PA (N = 5/15, 33%) and remained unchanged along follow-up. Thus, while being commonly observed in PA, hTERT promoter methylation is stable along follow-up and independent of most clinical variables, PA subtype, proliferation, and without prognostic value.