title: Decrease in vitamin D receptor and calcium-sensing receptor in highly proliferative parathyroid adenomas.
abstract: OBJECTIVE
  A significant decrease in vitamin D receptor (VDR) and calcium-sensing receptor (CaSR) protein expression has been demonstrated recently in parathyroid (PT) adenomas. In this study, we investigated the relationships between the proliferative activity of parathyroid glands (PTGs) and the expression of VDR as well as CaSR, and compared it with the clinical severity in patients with primary hyperparathyroidism (1 degrees HPT).
  
  
  METHODS
  Seven patients with 1 degrees HPT were included in this study. Four patients with thyroid carcinoma served as controls.
  
  
  METHODS
  Immunohistochemical staining was performed on serial sections of PTGs with specific antibodies against CaSR, VDR, and Ki67. Areas examined in each section were selected at random in relation to the gland size. The number of Ki67-positive cells was expressed as a labeling index (LI; positive cells per 1000 PT cells). The expression of CaSR and VDR was semi-quantitatively analyzed based on the intensity of staining. After averages of the scores from all areas were calculated, CaSR and VDR scores, and Ki67 LI were assigned to each gland for use in statistical analyses.
  
  
  RESULTS
  In PT adenomas, scores of VDR and CaSR were markedly lower than in normal PTGs (P<0.01), while the proportion of Ki67-positive cells in PT adenomas was significantly higher than in normal PTGs (P<0.01). Single regression analyses revealed that Ki67 LI was positively correlated with serum levels of intact parathyroid hormone and Ca, and PTG weight (R=0.70, P<0.05, R=0.78, P<0.01 and R=0.84, P<0.05 respectively). Ki67 LI was negatively correlated with CaSR and VDR scores (R=-0.78, P<0.01 and R=-0.72, P<0.05 respectively). Moreover, there was a strong positive relationship between CaSR and VDR expression (R=0.95, P<0.001).
  
  
  CONCLUSIONS
  Marked decreases in VDR and CaSR expression could, at least in part, be responsible for the high proliferation of PT cells and the pathological progression of 1 degree HPT.
authors.affiliation: Division of Endocrinology/Metabolism, Neurology, and Hematology/Oncology, Kobe University Graduate School of Medicine, Kobe, Japan. syano@rics.bwh.harvard.edu
authors.forename: Shozo
authors.initials: S
authors.lastname: Yano
authors.forename: Toshitsugu
authors.initials: T
authors.lastname: Sugimoto
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Tsukamoto
authors.forename: Kazuo
authors.initials: K
authors.lastname: Chihara
authors.forename: Akira
authors.initials: A
authors.lastname: Kobayashi
authors.forename: Sohei
authors.initials: S
authors.lastname: Kitazawa
authors.forename: Sakan
authors.initials: S
authors.lastname: Maeda
authors.forename: Riko
authors.initials: R
authors.lastname: Kitazawa
mesh_terms: D000236:Adenoma / Q000737:chemistry* / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002455:Cell Division; D006801:Humans; D006961:Hyperparathyroidism / Q000378:metabolism / Q000473:pathology; D015151:Immunoblotting; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008875:Middle Aged; D010280:Parathyroid Glands / Q000737:chemistry; D010282:Parathyroid Neoplasms / Q000737:chemistry* / Q000473:pathology*; D018167:Receptors, Calcitriol / Q000032:analysis*; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000032:analysis*; D012044:Regression Analysis
chemical_list: D019394:Ki-67 Antigen; D018167:Receptors, Calcitriol; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface