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Increase in Papillary Thyroid Cancer Incidence Is Accompanied by Changes in the Frequency of the BRAF V600E Mutation: A Single-Institution Study.
Thyroid. 2016 Apr; 26(4):543-51.T

Abstract

BACKGROUND

Thyroid cancer (TC) has one of the fastest increasing incidences worldwide and primarily involves papillary thyroid cancer (PTC). The BRAF(V600E) mutation is the most common genetic alteration identified in PTC. There are few data concerning an association between the rising incidence of PTC and the increasing prevalence of BRAF-positive cases. Environmental factors such as iodine intake may be responsible for the changing molecular features of PTC. The aim of this study was to evaluate probable variations in the frequency of the BRAF(V600E) mutation in PTC that were diagnosed at a single institution over 14 years in Poland, a country with a demonstrated improvement in iodine supplementation in the early 21st century.

METHODS

Time-dependent trends in the prevalence of the BRAF(V600E) mutation during three time periods (2000-2004, 2005-2009, and 2010-2013) were analyzed. The BRAF mutation was genotyped using direct sequencing, allele-specific polymerase chain reaction (PCR), and real-time PCR in 723 unselected cases of PTC that were diagnosed in 2000-2013. Trends in the clinicopathologic characteristics of all PTCs and BRAF(V600E)-positive PTCs were also analyzed.

RESULTS

The proportion of PTCs with mutations significantly increased over the study period (54.8% vs. 70.6%; p = 0.001). The median tumor size of all and BRAF-positive tumors decreased (p = 0.008 and p = 0.001, respectively) and correlated with an increase in the proportion of all and mutated microcarcinomas (p = 0.003 and p = 0.003, respectively). A decrease in all and mutated tumors between 2 and 4 cm was also observed (p = 0.002 and p = 0.006, respectively). A significant decrease in tumors ≥ 4 cm in size was only observed in BRAF-positive cases (p = 0.017). The proportion of classic PTC with BRAF(V600E) mutation was observed to increase (57.6% vs. 74.4%; p = 0.001) and was stable for the follicular variant of PTC (p = 0.336).

CONCLUSIONS

The prevalence of the BRAF(V600E)mutation increased significantly in PTCs diagnosed in the authors' institution. Improved detection and several causative factors, most likely environmental and changes in iodine intake, may contribute to the increasing occurrence of TC.

Authors+Show Affiliations

1 Department of Endocrinology, Holycross Cancer Centre , Kielce, Poland .1 Department of Endocrinology, Holycross Cancer Centre , Kielce, Poland .2 Department of Molecular Diagnostics, Holycross Cancer Centre , Kielce, Poland .1 Department of Endocrinology, Holycross Cancer Centre , Kielce, Poland .1 Department of Endocrinology, Holycross Cancer Centre , Kielce, Poland .3 Department of Surgical Pathology, Holycross Cancer Centre , Kielce, Poland .4 Department of Surgical Pathology, Medical University of Silesia , Katowice, Poland .5 Department of Probability Theory and Statistics Institute of Mathematics, Faculty of Mathematics and Natural Science, Jan Kochanowski University , Kielce, Poland .2 Department of Molecular Diagnostics, Holycross Cancer Centre , Kielce, Poland .2 Department of Molecular Diagnostics, Holycross Cancer Centre , Kielce, Poland .6 Department of Clinical Oncology, Holycross Cancer Centre , Kielce, Poland . 7 Faculty of Health Sciences, Jan Kochanowski University , Kielce, Poland .8 Department of Endocrinology and Nuclear Medicine, Military Institute of Medicine , Warsaw, Poland .

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26889698

Citation

Kowalska, Aldona, et al. "Increase in Papillary Thyroid Cancer Incidence Is Accompanied By Changes in the Frequency of the BRAF V600E Mutation: a Single-Institution Study." Thyroid : Official Journal of the American Thyroid Association, vol. 26, no. 4, 2016, pp. 543-51.
Kowalska A, Walczyk A, Kowalik A, et al. Increase in Papillary Thyroid Cancer Incidence Is Accompanied by Changes in the Frequency of the BRAF V600E Mutation: A Single-Institution Study. Thyroid. 2016;26(4):543-51.
Kowalska, A., Walczyk, A., Kowalik, A., Pałyga, I., Trybek, T., Kopczyński, J., Kajor, M., Chrapek, M., Pięciak, L., Chłopek, M., Góźdź, S., & Kamiński, G. (2016). Increase in Papillary Thyroid Cancer Incidence Is Accompanied by Changes in the Frequency of the BRAF V600E Mutation: A Single-Institution Study. Thyroid : Official Journal of the American Thyroid Association, 26(4), 543-51. https://doi.org/10.1089/thy.2015.0352
Kowalska A, et al. Increase in Papillary Thyroid Cancer Incidence Is Accompanied By Changes in the Frequency of the BRAF V600E Mutation: a Single-Institution Study. Thyroid. 2016;26(4):543-51. PubMed PMID: 26889698.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increase in Papillary Thyroid Cancer Incidence Is Accompanied by Changes in the Frequency of the BRAF V600E Mutation: A Single-Institution Study. AU - Kowalska,Aldona, AU - Walczyk,Agnieszka, AU - Kowalik,Artur, AU - Pałyga,Iwona, AU - Trybek,Tomasz, AU - Kopczyński,Janusz, AU - Kajor,Maciej, AU - Chrapek,Magdalena, AU - Pięciak,Liliana, AU - Chłopek,Małgorzata, AU - Góźdź,Stanisław, AU - Kamiński,Grzegorz, Y1 - 2016/02/18/ PY - 2016/2/19/entrez PY - 2016/2/19/pubmed PY - 2017/3/18/medline SP - 543 EP - 51 JF - Thyroid : official journal of the American Thyroid Association JO - Thyroid VL - 26 IS - 4 N2 - BACKGROUND: Thyroid cancer (TC) has one of the fastest increasing incidences worldwide and primarily involves papillary thyroid cancer (PTC). The BRAF(V600E) mutation is the most common genetic alteration identified in PTC. There are few data concerning an association between the rising incidence of PTC and the increasing prevalence of BRAF-positive cases. Environmental factors such as iodine intake may be responsible for the changing molecular features of PTC. The aim of this study was to evaluate probable variations in the frequency of the BRAF(V600E) mutation in PTC that were diagnosed at a single institution over 14 years in Poland, a country with a demonstrated improvement in iodine supplementation in the early 21st century. METHODS: Time-dependent trends in the prevalence of the BRAF(V600E) mutation during three time periods (2000-2004, 2005-2009, and 2010-2013) were analyzed. The BRAF mutation was genotyped using direct sequencing, allele-specific polymerase chain reaction (PCR), and real-time PCR in 723 unselected cases of PTC that were diagnosed in 2000-2013. Trends in the clinicopathologic characteristics of all PTCs and BRAF(V600E)-positive PTCs were also analyzed. RESULTS: The proportion of PTCs with mutations significantly increased over the study period (54.8% vs. 70.6%; p = 0.001). The median tumor size of all and BRAF-positive tumors decreased (p = 0.008 and p = 0.001, respectively) and correlated with an increase in the proportion of all and mutated microcarcinomas (p = 0.003 and p = 0.003, respectively). A decrease in all and mutated tumors between 2 and 4 cm was also observed (p = 0.002 and p = 0.006, respectively). A significant decrease in tumors ≥ 4 cm in size was only observed in BRAF-positive cases (p = 0.017). The proportion of classic PTC with BRAF(V600E) mutation was observed to increase (57.6% vs. 74.4%; p = 0.001) and was stable for the follicular variant of PTC (p = 0.336). CONCLUSIONS: The prevalence of the BRAF(V600E)mutation increased significantly in PTCs diagnosed in the authors' institution. Improved detection and several causative factors, most likely environmental and changes in iodine intake, may contribute to the increasing occurrence of TC. SN - 1557-9077 UR - https://www.unboundmedicine.com/medline/citation/26889698/Increase_in_Papillary_Thyroid_Cancer_Incidence_Is_Accompanied_by_Changes_in_the_Frequency_of_the_BRAF_V600E_Mutation:_A_Single_Institution_Study_ L2 - https://www.liebertpub.com/doi/full/10.1089/thy.2015.0352?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -