title: Relationship between cytokeratin staining patterns and clinico-pathological features in somatotropinomae.
abstract: OBJECTIVE
  Somatotropinomae are classified as densely and sparsely granulated adenomae, which typically exhibit a perinuclear pattern (PP) and a dot pattern (DP) in cytokeratin (CK) immunostaining respectively. Some exhibit a mixed pattern (MP). We studied the relationship between these somatotropinoma subtypes and their clinico-pathological features.
  
  
  METHODS
  The study population consisted of 141 Japanese acromegalic patients. We evaluated their clinical presentation and their response to provocation tests with TRH and LHRH and to suppression (octreotide) test. Tumour tissues were subjected to immunostaining for CAM-5.2, MIB-1, CD34, E-cadherin (CDH1) and p53 (TP53). In 43 cases (30 non-DP and 13 DP), we analysed gsp mutations (constitutively activating mutations of the G(s)α protein that is encoded by GNAS gene).
  
  
  RESULTS
  The 141 adenomae were categorised into three subtypes based on their CK staining patterns; 30 (21.3%) exhibited DP, 83 (58.9%) exhibited PP, and 28 (19.9%) exhibited MP. Compared with the other subtypes, DP adenomae were significantly larger, and their E-cadherin expression and response to TRH, LHRH and octreotide challenge were lower. The postoperative cure rate tended to be lower in DP adenomae. gsp mutations were detected in 25 of 43 cases examined (58.1%); 20 of the 30 non-DP (66.7%) and 5 of the 13 DP tumours (38.5%) were affected by the mutation.
  
  
  CONCLUSIONS
  DP somatotropinomae exhibit characteristic features. Compared with the non-DP subtypes, DP adenomae manifested a larger tumour size, a lower incidence of abnormal responses to TRH and LHRH challenge, a poor response to octreotide test and a lower expression of E-cadherin. gsp mutation was not exclusive for non-DP somatotropinomae.
authors.affiliation: Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka, Kagoshima, Japan.
authors.forename: Yuriz
authors.initials: Y
authors.lastname: Bakhtiar
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hirano
authors.forename: Kazunori
authors.initials: K
authors.lastname: Arita
authors.forename: Shunji
authors.initials: S
authors.lastname: Yunoue
authors.forename: Shingo
authors.initials: S
authors.lastname: Fujio
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tominaga
authors.forename: Tetsuhiko
authors.initials: T
authors.lastname: Sakoguchi
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Sugiyama
authors.forename: Kaoru
authors.initials: K
authors.lastname: Kurisu
authors.forename: Junko
authors.initials: J
authors.lastname: Yasufuku-Takano
authors.forename: Koji
authors.initials: K
authors.lastname: Takano
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D005260:Female; D013006:Growth Hormone / Q000097:blood; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000097:blood / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007633:Keratins / Q000378:metabolism*; D008297:Male; D008853:Microscopy; D008875:Middle Aged; D055815:Young Adult
chemical_list: D007334:Insulin-Like Growth Factor I; D007633:Keratins; D013006:Growth Hormone