Increased expression of HMGA1 correlates with tumour invasiveness and proliferation in human pituitary adenomas.
OBJECTIVE
High-mobility group A1 (HMGA1) is highly expressed in various benign and malignant tumours. The development of pituitary adenoma in Hmga1 transgenic mice has been reported. However, no studies have investigated HMGA1 expression and its clinical significance in human pituitary adenomas.


RESULTS
Immunohistochemical expression of HMGA1 was analysed with respect to various clinicopathological factors in 95 pituitary adenomas. Nuclear expression of HMGA1 was observed in 62% of pituitary adenomas, whereas normal adenohypophysial tissues were negative. Although HMGA1 expression was frequently detected in clinically non-functioning adenomas - 90% of silent adrenocorticotropic hormone (ACTH), 76.2% of follicle-stimulating hormone/luteinizing hormone and 100% of null cell adenomas - it was also detected in 48.1% of growth hormone (GH), 60% of mixed GH/prolactin (PRL), 62.5% of PRL, 66.6% of thyroid-stimulating hormone and 37.5% of ACTH adenomas. HMGA1 expression was significantly higher in invasive adenomas or macroadenomas than in non-invasive adenomas or microadenomas (invasive versus non-invasive, P < 0.05; macroadenoma versus microadenoma, P < 0.05). In addition, HMGA1 showed the highest level in grade IV, more aggressive pituitary adenomas, than in grades I, II and III (IV versus I, P = 0.01; IV versus II, P = 0.01; IV versus III, P = 0.07). Furthermore, a significant correlation between HMGA1 expression and MIB-1 labelling index was observed (R = 0.368, P < 0.0002).


CONCLUSIONS
These findings suggest that HMGA1 up-regulation has an important oncogenic role in pituitary tumorigenesis, as well as being a novel molecular marker of tumour proliferation and invasiveness.
Wang
Elaine Lu
EL
Department of Human Pathology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
Qian
Zhi Rong
ZR
Rahman
Md Mustafizur
MM
Yoshimoto
Katsuhiko
K
Yamada
Shozo
S
Kudo
Eiji
E
Sano
Toshiaki
T
D000236:Adenoma / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D016022:Case-Control Studies; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D005260:Female; D024003:HMGA Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness; D010911:Pituitary Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology*; D047368:Tumor Burden; D015854:Up-Regulation
D024003:HMGA Proteins