Immunohistochemical and Molecular Study of p16INK4A Expression in Pituitary Adenoma.

BACKGROUND AND OBJECTIVES: Pituitary adenomas comprise 10-25% of primary intracranial tumours. The molecular mechanisms underlying their development and progression have not yet been clearly defined. P16INK4A is frequently disrupted in human tumors including pituitary adenomas. Our aim was to evaluate the expression of P16 protein expression and its relation with gene methylation in pituitary adenoma development and progression.
MATERIAL AND METHODS: Immunohistochemistry was performed on 34 formalin fixed paraffin embedded specimens of pituitary adenoma. The p16INK4A gene methylation status was screened using an enzyme restricted polymerase chain reaction.
RESULTS: Loss of p16 protein expression occurred in 19/34 (55.9%) and P16INK4A methylation was detected in 14/34 (41.2%) of tumor samples. Both p16INK4A methylation and lack of p16 immunoreactivity were significantly related to larger tumor size and increased grade. Patients with either p16-negative or methylated tumors were significantly older than patients with p16-positive or unmethylated tumors. A significant positive correlation between loss of p16 protein expression and p16INK4A gene methylation was found.
CONCLUSION: These data suggest that p16 downregulation is a common event in pituitary adenoma and that its alteration might play an important role in genesis, growth progression, and biological behavior of pituitary adenomas. Our findings could imply that hypermethylation of the p16INK4A gene; represents the major target and perhaps a required epigenetic event in human pituitary tumorigenesis. KEY WORDS: Immunohistochemistry - Methylation - P16INK4A - Pituitary adenoma.