1. THE CHANGING DEMOGRAPHIC AND CLINICOPATHOLOGICAL CHARACTERISTICS AND MOLECULAR PROFILES OF PAPILLARY THYROID CARCINOMA OVER TIME: A SYSTEMATIC REVIEW
Huy Gia Vuong,1 Ahmed M.A. Altibi,2 Amr Hesham Abdelhamid,2 Phuong Uyen Duong Ngoc,2 Vo Duy Quan,2 Mohamed Yousef Tantawi,2 Mohamed Elfil,2 Tran Le Huy Vu,2 Ahmed Elgebaly,2 Naoki Oishi,1 Tadao Nakazawa,1 Kenji Hirayama,2 Ryohei Katoh,1 Nguyen Tien Huy,2 Tetsuo Kondo,1
1 Department of Pathology, University of Yamanashi, Yamanashi, Japan
2 Online Research Club
P2-298
INTRODUCTION
Over the last decades, incidence of thyroid cancer (especially papillary thyroid carcinoma (PTC)) has been increasing all over the world and the underlying causes are still continuously debated.
Prevalence of BRAF mutations were reported to increase over the years in a few single institutions.
In contrast, prevalence of RET/PTC rearrangements were shown to decrease over time.
RESULTS
Table 1. Trends of BRAF mutations in classical PTCs from individual institutions*
Abbreviations: NS, not significant; DS, direct sequencing; FMCA, fluorescent melting curve analysis; PS, pyrosequencing; AD, allelic discrimination
* Same detection methods were used for mutational analysis in different time periods
Table 2.Trends of RET/PTC in classical PTCs from individual institutions*
Abbreviations: DCI FISH, dual color interphase fluorescent in situ hybridization
Table 3. Trends of RAS mutations in classical PTCs from individual institutions*
Abbreviations: DS, direct sequencing; FMCA, fluorescent melting curve analysis
Country
City
Institution
Prevalence of BRAF mutations in classical PTCs (%)
Period 1
Period 2
Period 3
Period 4 P US
San Francisco
UCSF DS
42.7
88.2
<0.001
Pittsburgh
Univ. of Pittsburgh
50.0
FMCA
72.7
2009
77.0
0.011
Italy
Pisa/ Perugia/ Milan
Multicentre
37.5
62.2
52.9
0.012
Korea
Seoul
Seoul St. Mary’s Hospital
79.7
82.5 NS
64.9 PS
80.7
0.04
Ireland
Dublin
St. James’s Hospital
0.0
AD assay
73.3
0.043
AIMS OF OUR SYSTEMATIC REVIEW
To investigate the worldwide trends of BRAF mutations, RET/PTC rearrangements and RAS mutations in PTC
MATERIALS and METHODS
Literature search
Five electronic databases search: PubMed, Scopus, ISI Web of Science, World Health Organization Global Health Library (WHO GHL) and Virtual Health Library (VHL)
Key terms: (papillary thyroid AND (carcinoma OR cancer) AND (BRAF OR RAS OR RET/PTC)
Selection criteria
Inclusion criteria: articles containing data of BRAF, RET/PTC or RAS mutations in PTCs or classical PTCs
Exclusion criteria:
No information of institutions where the patients were treated
Focused on a specific parameter (e.g. pediatric PTCs, multifocal PTCs, recurrent PTCs)
Radiation-induced PTCs
Poster, proceeding paper, thesis, book, review, case report
Data extraction
Data analysis
Trends of BRAF, RET/PTC, RAS mutations in CLASSICAL PTCs in individual institutions
Trends of BRAF mutations in MICRO PTCs in individual institutions
Modifications and trends of clinicopathological characteristics of PTCs from individual institutions
Statistical analysis was analyzed by SPSS (version 22, Chicago, IL).
Country
City
Institution
Prevalence of RET/PTC in classical PTCs (%)
Period 1
Period 2
Period 3
Period 4 P US
San Francisco
UCSF
Nested PCR
18.4
3.9
0.047
Pittsburgh
Univ. of Pittsburgh
11.5
DCI FISH
5.6
2009
1.5 NS
Japan
Yamanashi
Univ. of Yamanashi
28.6
1.7
<0.001
Ireland
Dublin
St. James’s Hospital
66.7
RT-PCR
26.7
Country
City
Institution
Prevalence of RAS mutations in classical PTCs (%)
Period 1
Period 2
Period 3
Period 4 P US
San Francisco
UCSF DS
2.9
0.0 NS
Pittsburgh
Univ. of Pittsburgh
FMCA
2009
1.5
RESULTS (continued)
Table 4. Trends of BRAF mutations in micro PTCs from individual institutions*
Abbreviations: NS, not significant; DS, direct sequencing; FMCA, fluorescent melting curve analysis
* Same detection methods were used for mutational analysis in different periods
Table 5. Modifications of demographic and clinicopathological characteristics of PTCs over time from individual institutions
Abbreviations: FVPTC, follicular variant papillary thyroid carcinoma; ETE, extrathyroidal extension; LNM, Lymph node metastasis; NS, not significant; NA, not available; ND, not described
Country
City
Institution
Prevalence of BRAF mutations in micro PTCs (%)
Period 1
Period 2
Period 3
Period 4 P US
Pittsburgh
Univ. of Pittsburgh
32.3
FMCA
18.8
2009
38.0 NS
Korea
Seoul
Samsung Medical Centre
63.9 DS
75.8
0.013
China
Tianjin
Tianjin Medical Univ. Cancer Hospital
40.1
62.7
<0.001
Country
Institution
Period
Patients’ age (years) p
Male
(%)
Tumor size
FVPTC (%)
ETE
LNM US
University of Pittsburgh
2000
2009
Median, 37
Median, 50
Median, 53
<0.001
27.6
27.1
13.2
24.5 NS
≤1cm, 42.0
≤1cm, 44.1
≤1cm, 41.5
≤1cm, 51.3
10.2
3.4
25.2
40.2
26.9
20.9
0.005
26.8
28.8
20.8
18.3
Italy
University of Padua
01/ /2007
10/ /2009
Mean, 43.6*
Mean, 49
0.003
28.9
22.7 ND
≤1cm, 24.9 NA
3.6
3.5
45.4
51.8
38.3
0.049
Endocrine units of Pisa/Perugia/ Milan
Mean, 40.9
Mean, 44.0
Mean, 47.6
0.014
32.0
25.0
32.7
<2cm, 43.3
<2cm, 59.4
<2cm, 61.0
0.01
12.3
18.4
15.3
T3/T4, 45
T3/T4, 39
T3/T4, 35
50.7
48.1
51.9
Korea
Samsung Medical Centre
2008
Mean, 47.0
Mean, 48.0
18.5
16.9
≤1cm, 55.6
≤1cm, 80.5
2.9
62.2
53.5
36.5
0.043
CONCLUSION
The molecular profiles of PTCs have been changing over time: INCREASE of BRAF mutations and DECREASE of RET/PTC rearrangements.
The clinicopathological characteristics of PTCs have been changing over the years.
Our results suggests there have been modifications in the tumorigenesis of PTCs.
Conflicts of interest
The authors have no conflicts of interest regarding this poster presentation