Prognostic Significance of BRAF V600E Mutation and CPSF2 Protein Expression in Papillary Thyroid Cancer
The early-stage diagnosis of papillary thyroid cancer (PTC) has significantly increased in incidence worldwide without any beneficial impact on survival. In order to improve the risk assessment in PTC, we have conducted a retrospective study in which we analyzed the BRAF V600E mutation and CPSF2 pro...
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MDPI AG
2022-12-01
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| author | Irena Ivković Zgjim Limani Antonia Jakovčević Srećko Gajović Sven Seiwerth Ana Đanić Hadžibegović Drago Prgomet |
| author_facet | Irena Ivković Zgjim Limani Antonia Jakovčević Srećko Gajović Sven Seiwerth Ana Đanić Hadžibegović Drago Prgomet |
| author_sort | Irena Ivković |
| collection | DOAJ |
| description | The early-stage diagnosis of papillary thyroid cancer (PTC) has significantly increased in incidence worldwide without any beneficial impact on survival. In order to improve the risk assessment in PTC, we have conducted a retrospective study in which we analyzed the BRAF V600E mutation and CPSF2 protein expression as prognostic markers on archival tissue samples of 49 patients without (control group) and 97 patients with (study group) PTC metastases in the cervical lymph nodes at the time of initial diagnosis. Our aim was to correlate the BRAF V600E mutation and the expression of CPSF2 protein with the clinical and pathological features of PTC. The expression of CPSF2 protein was evaluated via immunohistochemistry and graded semi-quantitatively. The presence of the BRAF V600E mutation was determined via real-time polymerase chain reac-tion (PCR). CPSF2 protein < 3+ intensity expression was correlated with more frequent recurrences (Fisher-Freeman-Halton exact test; <i>p</i> = 0.010; 95% CI: 1.26–22.03), and patients who presented with the BRAF V600E mutation and CPSF2 protein expression < 3+ intensity had shorter disease-free survival (log-rank test; 105.0 months vs. 146.6 months; <i>p</i> < 0.001; HR 8.32, 95% CI: 2.91–23.83), whereas patients with PTC who had CPSF2 expression 3+ had longer disease-free survival in correlation with other lower intensity expressions of CPSF2 protein (log-rank test; 139.7 months vs. 129.6 months; <i>p</i> = 0.008). The multivariate analysis showed that younger patients with CPSF2 protein expression <3+ and the BRAF V600E mutation are at an increased risk for recurrence and require more intensive monitoring (Cox proportional hazards regression model; X2 = 17.5, df = 10, <i>p</i> = 0.025). Our results correlate the BRAF V600E mutation and CPSF2 protein expression with recurrence and disease-free survival as relevant prognostic factors for PTC. |
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| language | English |
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| spelling | doaj.art-73544806d7a74642abba4aa3f886fddf2023-11-30T21:18:45ZengMDPI AGBiomedicines2227-90592022-12-011115310.3390/biomedicines11010053Prognostic Significance of BRAF V600E Mutation and CPSF2 Protein Expression in Papillary Thyroid CancerIrena Ivković0Zgjim Limani1Antonia Jakovčević2Srećko Gajović3Sven Seiwerth4Ana Đanić Hadžibegović5Drago Prgomet6Department of Otorhinolaryngology-Head & Neck Surgery, University Hospital Centre Zagreb, 10 000 Zagreb, CroatiaDepartment of ENT-Head & Neck Surgery, University Clinical Center of Kosovo, 10 000 Prishtina, KosovoDepartment of Pathology and Cytology, University Hospital Centre Zagreb, 10 000 Zagreb, CroatiaCroatian Institute for Brain Research, School of Medicine, University of Zagreb, 10 000 Zagreb, CroatiaInstitute of Pathology, School of Medicine, University of Zagreb, 10 000 Zagreb, CroatiaDepartment of Otorhinolaryngology-Head & Neck Surgery, University Hospital Centre Zagreb, 10 000 Zagreb, CroatiaDepartment of Otorhinolaryngology-Head & Neck Surgery, University Hospital Centre Zagreb, 10 000 Zagreb, CroatiaThe early-stage diagnosis of papillary thyroid cancer (PTC) has significantly increased in incidence worldwide without any beneficial impact on survival. In order to improve the risk assessment in PTC, we have conducted a retrospective study in which we analyzed the BRAF V600E mutation and CPSF2 protein expression as prognostic markers on archival tissue samples of 49 patients without (control group) and 97 patients with (study group) PTC metastases in the cervical lymph nodes at the time of initial diagnosis. Our aim was to correlate the BRAF V600E mutation and the expression of CPSF2 protein with the clinical and pathological features of PTC. The expression of CPSF2 protein was evaluated via immunohistochemistry and graded semi-quantitatively. The presence of the BRAF V600E mutation was determined via real-time polymerase chain reac-tion (PCR). CPSF2 protein < 3+ intensity expression was correlated with more frequent recurrences (Fisher-Freeman-Halton exact test; <i>p</i> = 0.010; 95% CI: 1.26–22.03), and patients who presented with the BRAF V600E mutation and CPSF2 protein expression < 3+ intensity had shorter disease-free survival (log-rank test; 105.0 months vs. 146.6 months; <i>p</i> < 0.001; HR 8.32, 95% CI: 2.91–23.83), whereas patients with PTC who had CPSF2 expression 3+ had longer disease-free survival in correlation with other lower intensity expressions of CPSF2 protein (log-rank test; 139.7 months vs. 129.6 months; <i>p</i> = 0.008). The multivariate analysis showed that younger patients with CPSF2 protein expression <3+ and the BRAF V600E mutation are at an increased risk for recurrence and require more intensive monitoring (Cox proportional hazards regression model; X2 = 17.5, df = 10, <i>p</i> = 0.025). Our results correlate the BRAF V600E mutation and CPSF2 protein expression with recurrence and disease-free survival as relevant prognostic factors for PTC.https://www.mdpi.com/2227-9059/11/1/53papillary thyroid cancermetastasesCPSF2BRAF V600E mutationrecurrence |
| spellingShingle | Irena Ivković Zgjim Limani Antonia Jakovčević Srećko Gajović Sven Seiwerth Ana Đanić Hadžibegović Drago Prgomet Prognostic Significance of BRAF V600E Mutation and CPSF2 Protein Expression in Papillary Thyroid Cancer Biomedicines papillary thyroid cancer metastases CPSF2 BRAF V600E mutation recurrence |
| title | Prognostic Significance of BRAF V600E Mutation and CPSF2 Protein Expression in Papillary Thyroid Cancer |
| title_full | Prognostic Significance of BRAF V600E Mutation and CPSF2 Protein Expression in Papillary Thyroid Cancer |
| title_fullStr | Prognostic Significance of BRAF V600E Mutation and CPSF2 Protein Expression in Papillary Thyroid Cancer |
| title_full_unstemmed | Prognostic Significance of BRAF V600E Mutation and CPSF2 Protein Expression in Papillary Thyroid Cancer |
| title_short | Prognostic Significance of BRAF V600E Mutation and CPSF2 Protein Expression in Papillary Thyroid Cancer |
| title_sort | prognostic significance of braf v600e mutation and cpsf2 protein expression in papillary thyroid cancer |
| topic | papillary thyroid cancer metastases CPSF2 BRAF V600E mutation recurrence |
| url | https://www.mdpi.com/2227-9059/11/1/53 |
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