title: Increase in Papillary Thyroid Cancer Incidence Is Accompanied by Changes in the Frequency of the BRAF V600E Mutation: A Single-Institution Study.
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.affiliation: 1 Department of Endocrinology, Holycross Cancer Centre , Kielce, Poland .
authors.forename: Aldona
authors.initials: A
authors.lastname: Kowalska
authors.affiliation: 1 Department of Endocrinology, Holycross Cancer Centre , Kielce, Poland .
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Walczyk
authors.affiliation: 2 Department of Molecular Diagnostics, Holycross Cancer Centre , Kielce, Poland .
authors.forename: Artur
authors.initials: A
authors.lastname: Kowalik
authors.affiliation: 1 Department of Endocrinology, Holycross Cancer Centre , Kielce, Poland .
authors.forename: Iwona
authors.initials: I
authors.lastname: Pałyga
authors.affiliation: 1 Department of Endocrinology, Holycross Cancer Centre , Kielce, Poland .
authors.forename: Tomasz
authors.initials: T
authors.lastname: Trybek
authors.affiliation: 3 Department of Surgical Pathology, Holycross Cancer Centre , Kielce, Poland .
authors.forename: Janusz
authors.initials: J
authors.lastname: Kopczyński
authors.affiliation: 4 Department of Surgical Pathology, Medical University of Silesia , Katowice, Poland .
authors.forename: Maciej
authors.initials: M
authors.lastname: Kajor
authors.affiliation: 5 Department of Probability Theory and Statistics Institute of Mathematics, Faculty of Mathematics and Natural Science, Jan Kochanowski University , Kielce, Poland .
authors.forename: Magdalena
authors.initials: M
authors.lastname: Chrapek
authors.affiliation: 2 Department of Molecular Diagnostics, Holycross Cancer Centre , Kielce, Poland .
authors.forename: Liliana
authors.initials: L
authors.lastname: Pięciak
authors.affiliation: 2 Department of Molecular Diagnostics, Holycross Cancer Centre , Kielce, Poland .
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Chłopek
authors.affiliation: 6 Department of Clinical Oncology, Holycross Cancer Centre , Kielce, Poland .|7 Faculty of Health Sciences, Jan Kochanowski University , Kielce, Poland .
authors.forename: Stanisław
authors.initials: S
authors.lastname: Góźdź
authors.affiliation: 8 Department of Endocrinology and Nuclear Medicine, Military Institute of Medicine , Warsaw, Poland .
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Kamiński
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000453:epidemiology* / Q000235:genetics*; D002291:Carcinoma, Papillary; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006801:Humans; D015994:Incidence; D007455:Iodine / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011044:Poland; D016133:Polymerase Chain Reaction; D015995:Prevalence; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D013997:Time Factors; D055815:Young Adult
chemical_list: D007455:Iodine; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf