title: Diffuse parathyroid hormone expression in parathyroid tumors argues against important functional tumor subclones.
abstract: OBJECTIVE
  Primary hyperparathyroidism is usually characterized by a monoclonal parathyroid tumor secreting excess parathyroid hormone (PTH). The main regulator of PTH secretion is calcium and the calcium-PTH set point is shifted in parathyroid tumor cells. We sought to investigate the relationship between tumor PTH and PTH mRNA expression and clinical presentation as well as the regulatory factors including phosphate, vitamin D, and fibroblast growth factor 23.
  
  
  METHODS
  A total of 154 parathyroid tumors were analyzed by PTH immunohistochemistry and chromogenic in situ hybridization of PTH mRNA. A subset of samples (n = 34) was analyzed using quantitative real-time PCR.
  
  
  RESULTS
  Low tumor PTH mRNA level was significantly associated with low tumor PTH immunoreactivity (P = 0.026), but the two did not correlate with regard to histological distribution within individual tumors. Tumors displaying reduced PTH mRNA levels as compared with normal rim were significantly larger (P = 0.013) and showed higher expression of the calcium-sensing receptor (CASR) (P = 0.046). Weaker tumor PTH mRNA level was significantly associated with higher concentration of circulating 25-hydroxyvitamin D (P = 0.005). No significant correlation was seen between PTH immunoreactivity and patient biochemistry. Tumor weight was strongly associated with circulatory concentrations of calcium and PTH.
  
  
  CONCLUSIONS
  No areas with apparently higher PTH expression were identified, perhaps suggesting that hyper functioning parathyroid tumor subclones should be rare. Circulating 25-hydroxyvitamin D levels may influence tumor PTH expression in vivo. If PTH immunoreactivity reflects the tumor calcium-PTH set point, our data imply that the main determinant of disease severity should be tumor weight.
authors: Department of Oncology-PathologyKarolinska Institutet, Karolinska University Hospital CCK, SE-171 76 Stockholm, Sweden Felix.Haglund@ki.se.
authors: Felix
authors: F
authors: Haglund
authors: Department of Oncology-PathologyKarolinska Institutet, Karolinska University Hospital CCK, SE-171 76 Stockholm, Sweden.
authors: C Christofer
authors: CC
authors: Juhlin
authors: Department of Oncology-PathologyKarolinska Institutet, Karolinska University Hospital CCK, SE-171 76 Stockholm, Sweden.
authors: Nimrod B
authors: NB
authors: Kiss
authors: Department of Oncology-PathologyKarolinska Institutet, Karolinska University Hospital CCK, SE-171 76 Stockholm, Sweden.
authors: Catharina
authors: C
authors: Larsson
authors: Department of Molecular Medicine and SurgeryKarolinska Institutet, Karolinska University Hospital CCK, SE-171 76 Stockholm, Sweden.
authors: Inga-Lena
authors: IL
authors: Nilsson
authors: Department of Oncology-PathologyKarolinska Institutet, Karolinska University Hospital CCK, SE-171 76 Stockholm, Sweden.
authors: Anders
authors: A
authors: Höög
mesh_terms: D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000097:blood*; D015331:Cohort Studies; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D010281:Parathyroid Hormone / Q000378:metabolism*; D010282:Parathyroid Neoplasms / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D010281:Parathyroid Hormone; D012333:RNA, Messenger; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D002118:Calcium