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 1991-1995 51.4 DS 1996-2000 42.7 2001-2005 88.2   <0.001 Pittsburgh Univ. of Pittsburgh 1974-1985 50.0 FMCA 1990-1992 72.7 2000 70.8 2009 77.0 0.011 Italy Pisa/ Perugia/ Milan Multicentre 37.5 62.2 2006-2010 52.9 0.012 Korea Seoul Seoul St. Mary’s Hospital 2008-2009 79.7 2011-2012 82.5 NS 64.9 PS 2012-2013 80.7 0.04 Ireland Dublin St. James’s Hospital 1982-1992 0.0 AD assay 1993-2002 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 1991-1995 13.5 Nested PCR 1996-2000 18.4 2001-2005 3.9   0.047 Pittsburgh Univ. of Pittsburgh 1974-1985 11.5 DCI FISH 1990-1992 5.6 2000 8.7 2009 1.5 NS Japan Yamanashi Univ. of Yamanashi 2001-2006 28.6 2011-2014 1.7 <0.001 Ireland Dublin St. James’s Hospital 1982-1992 66.7 RT-PCR 1993-2002 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 1991-1995 4.1 DS 1996-2000 2.9 2001-2005 0.0   NS Pittsburgh Univ. of Pittsburgh 1974-1985 FMCA 1990-1992 2000 0.0 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 1974-1985 32.3 FMCA 1990-1992 18.8 2000 23.5 2009 38.0 NS Korea Seoul Samsung Medical Centre 2008-2009 63.9 DS 2010-2011 75.8   0.013 China Tianjin Tianjin Medical Univ. Cancer Hospital 2001-2010 40.1 2013-2014 62.7 <0.001 Country Institution Period Patients’ age (years) p Male (%) Tumor size FVPTC (%) ETE LNM US University of Pittsburgh 1974-1985 1990-1992 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 01/2005-07/2007 10/2008-09/2009 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 1996-2000 2001-2005 2006-2010 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 2010-2011 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