hTERT promoter methylation in pituitary adenomas

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.