P53 protein accumulates in Cushings adenomas and invasive non-functional adenomas.
The p53 protein, a negative regulator of cell growth, plays an important role in the pathogenesis of many human tumours following gene mutation and/or deletion. We screened a large number of sporadic pituitary tumours for p53 protein accumulation suggestive of gene mutation. Samples were divided into benign adenomas (n = 95) and invasive tumours with local or distant invasion (n = 26). All main tumour classes were represented. Putative p53 mutations were detected by immunohistochemistry on paraffin-embedded sections using polyclonal CM-1 and monoclonal DO-7 and PAb1801 antibodies. Results were compared to normal post-mortem pituitary tissue controls (n = 17). p53 protein accumulation was detected in invasive tumours (16%), but only in corticotrophinomas (2/4) and non-functional tumours (4/15). In non-invasive adenomas, protein accumulation was observed only in ACTH-secreting tumours where 50% were positive (16/32). No protein accumulation was identified in any control tissue. These results indicate that p53 protein accumulation may play a role in the development of Cushings adenomas and in the progression of non-functional tumours to the invasive state.
School of Postgraduate Medicine, Keele University, North Staffordshire Hospital Centre, Stoke on Trent, UK.
N
N
Buckley
A S
AS
Bates
J C
JC
Broome
R C
RC
Strange
C W
CW
Perrett
C W
CW
Burke
R N
RN
Clayton
D000236:Adenoma / Q000737:chemistry / Q000209:etiology / Q000378:metabolism*; D000237:Adenoma, Basophil / Q000737:chemistry / Q000209:etiology / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D010911:Pituitary Neoplasms / Q000737:chemistry / Q000209:etiology / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53; D000324:Adrenocorticotropic Hormone