Association of BRAF V600E Mutant Allele Proportion with the Dissemination Stage of Papillary Thyroid Cancer

被引:1
作者
Blazekovic, Ivan [1 ,2 ]
Samija, Ivan [1 ,3 ]
Perisa, Josipa [1 ]
Troselj, Koraljka Gall [4 ]
Dzombeta, Tihana Regovic [5 ,6 ]
Radulovic, Petra [5 ]
Romic, Matija [1 ]
Granic, Roko [1 ]
Markos, Ines Sisko [1 ,2 ]
Frobe, Ana [1 ,3 ]
Kusic, Zvonko [7 ]
Jukic, Tomislav [1 ,6 ,8 ]
机构
[1] Univ Hosp Ctr Sestre Milosrdnice, Dept Oncol & Nucl Med, Zagreb 10000, Croatia
[2] Catholic Univ Croatia, Sch Med, Zagreb 10000, Croatia
[3] Univ Zagreb, Sch Dent Med, Zagreb 10000, Croatia
[4] Rudjer Boskovic Inst, Div Mol Med, Lab Epigen, Zagreb 10000, Croatia
[5] Univ Hosp Ctr Sestre Milosrdnice, Dept Pathol Ljudevit Jurak, Zagreb, Croatia
[6] Univ Zagreb, Sch Med, Zagreb 10000, Croatia
[7] Croatian Acad Sci & Arts, Zagreb 10000, Croatia
[8] Josip Juraj Strossmayer Univ Osijek, Fac Med Osijek, Osijek, Croatia
关键词
papillary thyroid cancer; dissemination; BRAF V600E; tumor heterogeneity; qPCR; TERT PROMOTER MUTATIONS; CARCINOMA; BRAF(V600E); PERCENTAGE; PREDICTS; METASTASES; MORTALITY; SYSTEM;
D O I
10.3390/biomedicines12030477
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The early identification of aggressive forms of cancer is of high importance in treating papillary thyroid cancer (PTC). Disease dissemination is a major factor influencing patient survival. Mutation status of BRAF oncogene, BRAF V600E, is proposed to be an indicator of disease recurrence; however, its influence on PTC dissemination has not been deciphered. This study aimed to explore the association of the frequency of BRAF V600E alleles in PTC with disease dissemination. In this study, 173 PTC samples were analyzed, measuring the proportion of BRAF V600E alleles by qPCR, which was then normalized against the proportion of tumor cells. Semiquantitative analysis of BRAF V600E mutant protein was performed by immunohistochemistry. The BRAF V600E mutation was present in 60% of samples, while the normalized frequency of mutated BRAF alleles ranged from 1.55% to 92.06%. There was no significant association between the presence and/or proportion of the BRAF V600E mutation with the degree of PTC dissemination. However, the presence of the BRAF mutation was significantly linked with angioinvasion. This study's results suggest that there is a heterogeneous distribution of the BRAF mutation and the presence of oligoclonal forms of PTC. It is likely that the BRAF mutation alone does not significantly contribute to PTC aggressiveness.
引用
收藏
页数:12
相关论文
共 50 条
[31]   Structural insights and influence of V599 mutations on the overall dynamics of BRAF protein against its kinase domains [J].
Mayank ;
Kaur, Navneet ;
Singh, Narinder .
INTEGRATIVE BIOLOGY, 2018, 10 (10) :646-657
[32]   Telomerase Reverse Transcriptase (TERT) Regulation in Thyroid Cancer: A Review [J].
McKelvey, Brittany A. ;
Umbricht, Christopher B. ;
Zeiger, Martha A. .
FRONTIERS IN ENDOCRINOLOGY, 2020, 11
[33]   Clinical implication of hot spot BRAF mutation, V599E, in papillary thyroid cancers [J].
Namba, H ;
Nakashima, M ;
Hayashi, T ;
Hayashida, N ;
Maeda, S ;
Rogounovitch, TI ;
Ohtsuru, A ;
Saenko, VA ;
Kanematsu, T ;
Yamashita, S .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2003, 88 (09) :4393-4397
[34]   Thyroid carcinoma: molecular pathways and therapeutic targets [J].
Nikiforov, Yuri E. .
MODERN PATHOLOGY, 2008, 21 :S37-S43
[35]   Molecular genetics and diagnosis of thyroid cancer [J].
Nikiforov, Yuri E. ;
Nikiforova, Marina N. .
NATURE REVIEWS ENDOCRINOLOGY, 2011, 7 (10) :569-580
[36]   CLONAL EVOLUTION OF TUMOR-CELL POPULATIONS [J].
NOWELL, PC .
SCIENCE, 1976, 194 (4260) :23-28
[37]   Worldwide Increasing Incidence of Thyroid Cancer: Update on Epidemiology and Risk Factors [J].
Pellegriti, Gabriella ;
Frasca, Francesco ;
Regalbuto, Concetto ;
Squatrito, Sebastiano ;
Vigneri, Riccardo .
JOURNAL OF CANCER EPIDEMIOLOGY, 2013, 2013
[38]   BRAF (V600E) mutation analysis on liquid-based cytology-processed aspiration biopsies predicts bilaterality and lymph node involvement in papillary thyroid microcarcinoma [J].
Rossi, Esther Diana ;
Martini, Maurizio ;
Capodimonti, Sara ;
Lombardi, Celestino Pio ;
Pontecorvi, Alfredo ;
Vellone, Valerio Gaetano ;
Zannoni, Gian Franco ;
Larocca, Luigi Maria ;
Fadda, Guido .
CANCER CYTOPATHOLOGY, 2013, 121 (06) :291-297
[39]   Detection of BRAF mutation in thyroid papillary carcinomas by mutant allele-specific PCR amplification (MASA) [J].
Sapio, MR ;
Posca, D ;
Troncone, G ;
Pettinato, G ;
Palombini, L ;
Rossi, G ;
Fenzi, G ;
Vitale, M .
EUROPEAN JOURNAL OF ENDOCRINOLOGY, 2006, 154 (02) :341-348
[40]   Nuclear features of papillary thyroid carcinoma: Comparison of Core needle biopsy and thyroidectomy specimens [J].
Seok, Jae Yeon ;
An, Jungsuk ;
Cho, Hyun Yee ;
Kim, Younghye ;
Ha, Seung Yeon .
ANNALS OF DIAGNOSTIC PATHOLOGY, 2018, 32 :35-40