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Vitamin D-neutralizing CYP24A1 expression, oncogenic mutation states and histological findings of human papillary thyroid cancer

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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.

Materials and 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.

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Acknowledgments

The authors are indebted to Kalocsáné Piurkó Violetta (2nd Department of Pathology, Semmelweis University) for excellent technical assistance of paraffin-embedded tissue specimens. We would like to thank to Béla Iványi (Faculty of General Medicine, Department of Pathology, University of Szeged) who provided paraffin-embedded tissue samples. This work was supported by research Grant ETT 10-151/2009 from the Ministry of Health, Hungary.

Conflict of interest

All the authors state that they have no conflicts of interest.

Author information

Authors and Affiliations

  1. 1st Department of Internal Medicine, Semmelweis University, Korányi S. u. 2/a, Budapest, 1083, Hungary

    B. Balla, B. Tobiás, J. P. Kósa, P. Horváth, Z. Nagy, K. Árvai, M. Dank, Z. Putz, B. Szabó, B. Szili, P. Lakatos & I. Takács

  2. Biological Institute, Eötvös Loránd University, Pázmány Péter stny. 1/c, Budapest, 1117, Hungary

    J. Podani

  3. 1st Department of Surgery, Semmelweis University, Üllői út 78, Budapest, 1082, Hungary

    J. Horányi

  4. 2nd Department of Pathology, Semmelweis University, Üllői út 93, Budapest, 1091, Hungary

    B. Járay & E. Székely

  5. Laboratory of Tumor Pathology and Molecular Diagnostics, Jobb fasor 23/b, Szeged, 6726, Hungary

    L. Krenács

  6. 1st Department of Internal Medicine, University of Szeged, Korányi fasor 8-10, Szeged, 6720, Hungary

    Z. Valkusz

  7. Department of Pathology, Faculty of General Medicine, University of Szeged, Állomás u. 2, Szeged, 6720, Hungary

    B. Vasas

  8. Department of Radiology and Oncotherapy, Semmelweis University, Üllői út 78/a, Budapest, 1082, Hungary

    G. Győri

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  1. B. Balla
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  2. B. Tobiás
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  3. J. P. Kósa
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  4. J. Podani
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  19. P. Lakatos
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Corresponding author

Correspondence to B. Balla.

Additional information

B. Balla, B. Tobiás, P. Lakatos and I. Takács contributed equally to this work.

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Balla, B., Tobiás, B., Kósa, J.P. et al. Vitamin D-neutralizing CYP24A1 expression, oncogenic mutation states and histological findings of human papillary thyroid cancer. J Endocrinol Invest 38, 313–321 (2015). https://doi.org/10.1007/s40618-014-0165-7

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  • DOI: https://doi.org/10.1007/s40618-014-0165-7

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