Related Experiment Videos
CDKN2A/p16 inactivation is related to pituitary adenoma type and size
N Seemann1, D Kuhn, C Wrocklage
1Institute of Neuropathology, University of Münster, Domagkstrasse 19, D-48129 Münster, Germany.
Abstract:
p16 (CDKN2A, MTS1, INK4A) status at genomic and protein levels was analysed and correlated with clinico-pathological features in 72 pituitary adenomas. Methylation of CpG islands of promoter/exon 1 sequences was found in most gonadotroph, lactotroph, plurihormonal, and null cell adenomas (36 of 44, 82%), but it was rare in somatotroph (1 of 13 cases, 8%) and corticotroph adenomas (1 of 15 cases, 7%). Homozygous CDKN2A deletion was restricted to rare somatotroph (15%) and corticotroph adenomas (13%). Immunohistochemical p16 protein expression was observed in the normal adenohypophysis, whereas it was absent in 60 of 72 (83%) tumours and reduced in another ten (14%) tumours. Staining for p16 was only seen in 5 of 15 (33%) corticotroph, 3 of 13 (23%) somatotroph, 3 of 5 (60%) plurihormonal, and 1 of 19 (5%) null cell adenomas. p16 immunonegativity without CDKN2A methylation or deletion occurred in 22 tumours, including most somatotroph and corticotroph adenomas (15 of 28, 54%). Both CDKN2A alterations and p16 negativity were related to larger tumour size. Patients with p16-negative tumours were older than patients with p16-positive tumours. These data suggest that p16 down-regulation is common in all adenoma types. The mechanisms of p16 down-regulation probably involve CDKN2A methylation in most types, but remain to be determined in somatotroph and corticotroph adenomas. These findings also suggest that p16 down-regulation is usually not an initial event, but is acquired during adenoma progression.
Insights
p16 protein down-regulation is common in pituitary adenomas, often linked to larger tumor size and older patients. Mechanisms involve CDKN2A methylation, but require further study in specific adenoma types.
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- p16 (CDKN2A) is a tumor suppressor gene.
- Its role in pituitary adenomas is not fully understood.
- Pituitary adenomas are common tumors of the pituitary gland.
Purpose of the Study:
- To analyze p16 status at genomic and protein levels in pituitary adenomas.
- To correlate p16 alterations with clinico-pathological features.
- To investigate the mechanisms of p16 down-regulation.
Main Methods:
- Analysis of p16 (CDKN2A) methylation and homozygous deletion in 72 pituitary adenomas.
- Immunohistochemical analysis of p16 protein expression.
- Correlation of molecular findings with tumor size and patient age.
Main Results:
- p16 down-regulation (methylation or deletion) was frequent in most adenoma types, except somatotroph and corticotroph adenomas.
- p16 protein was absent or reduced in 97% of tumors.
- CDKN2A alterations and p16 negativity correlated with larger tumor size and older patient age.
Conclusions:
- p16 down-regulation is a common event in pituitary adenomas, suggesting a role in tumorigenesis.
- CDKN2A methylation is a likely mechanism in most adenoma types.
- Further research is needed to elucidate p16 regulation in somatotroph and corticotroph adenomas.
- p16 down-regulation appears to be acquired during adenoma progression.