title: Vitamin D-neutralizing CYP24A1 expression, oncogenic mutation states and histological findings of human papillary thyroid cancer.
abstract: OBJECTIVE
  The aims of the present study were to examine gene and protein expression of the vitamin D-inactivating 24-hyroxylase (CYP24A1) and the activating 1-alpha-hydroxylase (CYP27B1) enzyme in human papillary thyroid cancer (PTC), furthermore, to investigate the association between CYP24A1 expression and numerous clinical, histological parameters and somatic oncogene mutation status of thyroid tumor tissues.
  
  
  METHODS
  Gene expression analysis was carried out in 100 Hungarian thyroid samples, both normal and papillary tumor tissue sections of the same patient. The specific mRNA to the selected genes was analyzed by TaqMan probe-based quantitative real-time RT-PCR. The somatic oncogene mutation states of BRAF, NRAS, HRAS and KRAS were also tested.
  
  
  RESULTS
  CYP24A1 mRNA expression was markedly increased in 52 cases (52%) of the examined papillary cancers compared with that of normal thyroid tissue. There was a tendency toward difference in the distribution of high-level CYP24A1 in the PTC accompanied with somatic oncogene mutation. Positive correlation was seen between increased CYP24A1 expression rate and a group of variables reflecting tumor malignity (mainly vascular invasion, lymph node metastasis, tumor size, hypothyreosis) by principal components analysis. No significant alteration was seen in CYP27B1 gene expression between neoplastic and normal tissues.
  
  
  CONCLUSIONS
  A definite alteration was seen in vitamin D3-inactivating CYP24A1 gene activity in PTC compared to their normal tissues on a relatively large patient population. Our findings raise the possibility that CYP24A1 may also directly be involved in thyroid carcinogenesis.
authors.affiliation: 1st Department of Internal Medicine, Semmelweis University, Korányi S. u. 2/a, Budapest, 1083, Hungary. balladetti@gmail.com.
authors.forename: B
authors.initials: B
authors.lastname: Balla
authors.affiliation: 1st Department of Internal Medicine, Semmelweis University, Korányi S. u. 2/a, Budapest, 1083, Hungary.
authors.forename: B
authors.initials: B
authors.lastname: Tobiás
authors.affiliation: 1st Department of Internal Medicine, Semmelweis University, Korányi S. u. 2/a, Budapest, 1083, Hungary.
authors.forename: J P
authors.initials: JP
authors.lastname: Kósa
authors.affiliation: Biological Institute, Eötvös Loránd University, Pázmány Péter stny. 1/c, Budapest, 1117, Hungary.
authors.forename: J
authors.initials: J
authors.lastname: Podani
authors.affiliation: 1st Department of Internal Medicine, Semmelweis University, Korányi S. u. 2/a, Budapest, 1083, Hungary.
authors.forename: P
authors.initials: P
authors.lastname: Horváth
authors.affiliation: 1st Department of Internal Medicine, Semmelweis University, Korányi S. u. 2/a, Budapest, 1083, Hungary.
authors.forename: Z
authors.initials: Z
authors.lastname: Nagy
authors.affiliation: 1st Department of Surgery, Semmelweis University, Üllői út 78, Budapest, 1082, Hungary.
authors.forename: J
authors.initials: J
authors.lastname: Horányi
authors.affiliation: 2nd Department of Pathology, Semmelweis University, Üllői út 93, Budapest, 1091, Hungary.
authors.forename: B
authors.initials: B
authors.lastname: Járay
authors.affiliation: 2nd Department of Pathology, Semmelweis University, Üllői út 93, Budapest, 1091, Hungary.
authors.forename: E
authors.initials: E
authors.lastname: Székely
authors.affiliation: Laboratory of Tumor Pathology and Molecular Diagnostics, Jobb fasor 23/b, Szeged, 6726, Hungary.
authors.forename: L
authors.initials: L
authors.lastname: Krenács
authors.affiliation: 1st Department of Internal Medicine, Semmelweis University, Korányi S. u. 2/a, Budapest, 1083, Hungary.
authors.forename: K
authors.initials: K
authors.lastname: Árvai
authors.affiliation: 1st Department of Internal Medicine, Semmelweis University, Korányi S. u. 2/a, Budapest, 1083, Hungary.
authors.forename: M
authors.initials: M
authors.lastname: Dank
authors.affiliation: 1st Department of Internal Medicine, Semmelweis University, Korányi S. u. 2/a, Budapest, 1083, Hungary.
authors.forename: Z
authors.initials: Z
authors.lastname: Putz
authors.affiliation: 1st Department of Internal Medicine, Semmelweis University, Korányi S. u. 2/a, Budapest, 1083, Hungary.
authors.forename: B
authors.initials: B
authors.lastname: Szabó
authors.affiliation: 1st Department of Internal Medicine, Semmelweis University, Korányi S. u. 2/a, Budapest, 1083, Hungary.
authors.forename: B
authors.initials: B
authors.lastname: Szili
authors.affiliation: 1st Department of Internal Medicine, University of Szeged, Korányi fasor 8-10, Szeged, 6720, Hungary.
authors.forename: Z
authors.initials: Z
authors.lastname: Valkusz
authors.affiliation: Department of Pathology, Faculty of General Medicine, University of Szeged, Állomás u. 2, Szeged, 6720, Hungary.
authors.forename: B
authors.initials: B
authors.lastname: Vasas
authors.affiliation: Department of Radiology and Oncotherapy, Semmelweis University, Üllői út 78/a, Budapest, 1082, Hungary.
authors.forename: G
authors.initials: G
authors.lastname: Győri
authors.affiliation: 1st Department of Internal Medicine, Semmelweis University, Korányi S. u. 2/a, Budapest, 1083, Hungary.
authors.forename: P
authors.initials: P
authors.lastname: Lakatos
authors.affiliation: 1st Department of Internal Medicine, Semmelweis University, Korányi S. u. 2/a, Budapest, 1083, Hungary.
authors.forename: I
authors.initials: I
authors.lastname: Takács
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D065668:Vitamin D3 24-Hydroxylase / Q000235:genetics*; D055815:Young Adult; D018631:ras Proteins / Q000235:genetics
chemical_list: D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D048493:Proto-Oncogene Proteins B-raf; D018631:ras Proteins
keywords: CYP24A1; Gene expression; Multivariate data analysis; Papillary thyroid carcinoma; Vitamin D