title: Increased expression of HMGA1 correlates with tumour invasiveness and proliferation in human pituitary adenomas.
abstract: 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.
authors.affiliation: Department of Human Pathology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Elaine Lu
authors.initials: EL
authors.lastname: Wang
authors.forename: Zhi Rong
authors.initials: ZR
authors.lastname: Qian
authors.forename: Md Mustafizur
authors.initials: MM
authors.lastname: Rahman
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Yoshimoto
authors.forename: Shozo
authors.initials: S
authors.lastname: Yamada
authors.forename: Eiji
authors.initials: E
authors.lastname: Kudo
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sano
mesh_terms: 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
chemical_list: D024003:HMGA Proteins