title: Immunohistochemical detection of cell cycle regulators, Fhit protein and apoptotic cells in parathyroid lesions.
abstract: OBJECTIVE
  The pathological distinction between parathyroid neoplasms and hyperplasias remains difficult. Changes in cell cycle control may lead to clonal proliferation and precede tumorigenesis. The parathyroid adenoma 1 oncogene, subsequently identified as the gene encoding cyclin D1, has been shown to be important to parathyroid tumour development. In addition to cell proliferation, the mechanisms of parathyroid cell turnover include apoptosis. The tumour-suppressor activity of the fragile histidine triad gene (FHIT) is linked to its proapoptotic function and cell cycle control. We attempted to evaluate the cellular proliferative kinetics and apoptotic function of the parathyroid glands in patients with non-familial hyperparathyroidism (HPT).
  
  
  METHODS
  TIssue specimens were taken from 40 patients with primary HPT (17 adenomas, two carcinomas and 21 primary hyperplasias) and from 30 patients with secondary HPT. Normal glands served as controls.
  
  
  METHODS
  In a standard immunohistochemical procedure, monoclonal antibodies to Ki-67 antigen and single-stranded DNA were applied to detect cycling and apoptotic cells respectively; polyclonal antibodies to cyclin D1 and Fhit protein were used. Immunostaining was estimated by image analysis and statistical analysis was subsequently performed.
  
  
  RESULTS
  Significantly higher proliferative and apoptotic indexes were detected in the diseased glands in comparison with normal controls. In neoplastic and secondarily hyperplastic glands, apoptotic indexes were higher than in primarily hyperplastic glands; the difference between neoplastic and primarily hyperplastic glands was statistically significant (P=0.034). Cyclin D1 was overexpressed in a considerable proportion of tumours (68.4%). A reduction of Fhit protein immunoreactivity was selectively noticed in carcinomas.
  
  
  CONCLUSIONS
  In primary hyperplasia, the remarkable proliferation of parathyroid glands may be due to the reduction of the apoptotic process. FHIT gene abnormalities are worthy of investigation in parathyroid carcinogenesis.
authors.affiliation: Department of Pathology, School of Medicine, The Athens National and Kapodistrian University, Athens, Greece.
authors.forename: G-E
authors.initials: GE
authors.lastname: Thomopoulou
authors.forename: S
authors.initials: S
authors.lastname: Tseleni-Balafouta
authors.forename: A C
authors.initials: AC
authors.lastname: Lazaris
authors.forename: H
authors.initials: H
authors.lastname: Koutselini
authors.forename: N
authors.initials: N
authors.lastname: Kavantzas
authors.forename: P S
authors.initials: PS
authors.lastname: Davaris
mesh_terms: D017766:Acid Anhydride Hydrolases; D000236:Adenoma / Q000737:chemistry / Q000473:pathology; D017209:Apoptosis; D002277:Carcinoma / Q000737:chemistry / Q000473:pathology; D002453:Cell Cycle; D005260:Female; D006801:Humans; D006961:Hyperparathyroidism / Q000473:pathology*; D006965:Hyperplasia; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D010280:Parathyroid Glands / Q000737:chemistry* / Q000473:pathology*; D010282:Parathyroid Neoplasms / Q000737:chemistry / Q000473:pathology; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase