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 a
denomas (1 of 15 cases, 7%). Homozygous CDKN2A deletion was restricted to r
are 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%) rumours and reduced in another ten (14%) t
umours, 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 cel
l adenomas, p16 immunonegativity without CDKN2A methylation or deletion occ
urred 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 rumours were older than pati
ents with p16-positive tumours, These data suggest that p16 down-regulation
is common in all adenoma types. The mechanisms of p16 down-regulation prob
ably 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. Copyright (C) 2001 John Wiley & Sons, Ltd.