Oncogene-induced senescence in pituitary adenomas and carcinomas.
OBJECTIVE
The model of "oncogene-induced senescence" (OIS), resulting in cell-proliferation arrest, has recently been suggested as a possible explanation for the non-progression of pituitary tumours to malignancy. The aim of the study was to compare the expression of β-galactosidase as a molecular marker of OIS, and p21/p16 as additional markers involved in mediating OIS, in pituitary adenomas, carcinomas and normal pituitary tissue.


METHODS
We performed: a) semi-quantitative immunohistochemistry (β-galactosidase, p16, p21) in 41 pituitary adenomas [(11 GH-secreting, 9 PRL-secreting, 10 ACTH-secreting, 11 non-functioning (NFPAs)], 6 carcinomas (3 multihormonal: PRL/ACTH/GH, PRL/ACTH, PRL/GH/FSH; 1 non-functioning; 2 ACTH-secreting) and 7 normal pituitary tissues; b) quantitative PCR of mRNA (p16 and p21) in 6 GH-secreting, 6 NFPAs and 6 normal pituitary tissues.


RESULTS
β-galactosidase was significantly increased in GH-secreting tumours (P=0.002), NFPAs (P=0.04), macroadenomas (P=0.03) and carcinomas (P=0.02), as compared to normal pituitary tissue. We found that p16 expression was significantly lower in all tumours (both adenomas and carcinomas) probably secondary to reduced transcription, at least for NFPAs; p21 showed a different biological behaviour, implying that p21 and p16 may play different roles in the senescence of each individual type of adenoma.


CONCLUSIONS
β-galactosidase was significantly over-expressed in GH-secreting and NFPAs, and unexpectedly also in carcinomas. We speculate that the senescence pathway, which may explain the rarity of malignant progression to carcinomas in GH-secreting and NFPAs, might not be universal but cell-type specific.
Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine, London, U.K.
Krystallenia I
KI
Alexandraki
Mohammed
M
Munayem Khan
Harvinder S
HS
Chahal
Nadezhda S
NS
Dalantaeva
Giampaolo
G
Trivellin
Dan M
DM
Berney
Philippe
P
Caron
Vera
V
Popovic
Marija
M
Pfeifer
Suzanne
S
Jordan
Márta
M
Korbonits
Ashley B
AB
Grossman
D000236:Adenoma / Q000378:metabolism / Q000503:physiopathology*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000375:Aging; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis; D013006:Growth Hormone / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D010902:Pituitary Gland / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D015175:Prolactinoma / Q000378:metabolism; D001616:beta-Galactosidase / Q000096:biosynthesis*
D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D000324:Adrenocorticotropic Hormone; D013006:Growth Hormone; D001616:beta-Galactosidase