The Prognostic Significance of BRAF Gene Analysis in Children and Adolescents with Papillary Thyroid Carcinoma: A Systematic Review and Meta-Analysis

Abstract

Thyroid cancer represents the prominent endocrine cancer in children. Papillary thyroid cancer (PTC) constitutes its most frequent (>90%) pediatric histological type. Mutations energizing the mitogen-activated-protein kinase (MAPK) pathway are definitely related to PTC. Its most common genetic alteration is in proto-oncogene B-Raf (BRAF). Mutated BRAF is proposed as a prognostic tool in adult PTC. We conducted a systematic review and meta-analysis evaluating the association of mutated BRAF gene and prognostic clinicopathological characteristics of PTC in children/adolescents. Systematic search for relevant studies included PubMed, MEDLINE, Scopus, clinicaltrials.gov and Cochrane Library. Pooled estimates of odds ratios for categorical data and mean difference for continuous outcomes were calculated using random/fixed-effect meta-analytic models. BRAFV600E mutation presents a pooled pediatric/adolescent prevalence of 33.12%. Distant metastasis is significantly associated with mutated BRAF gene (OR = 0.32, 95% CI = 0.16–0.61, p = 0.001). Tumor size (MD = −0.24, 95% CI = −0.62–0.135, p = 0.21), multifocality (OR = 1.13, 95% CI = 0.65–2.34, p = 0.74), vascular invasion (OR = 1.17, 95% CI = 0.67–2.05, p = 0.57), lymph node metastasis (OR = 0.92, 95% CI = 0.63–1.33, p = 0.66), extra-thyroid extension (OR = 0.78, 95% CI = 0.53–1.13, p = 0.19) and tumor recurrence (OR = 1.66, 95% CI = 0.68–4.21, p = 0.376) presented no association or risk with BRAF mutation among pediatric/adolescent PTC. Mutated BRAF gene in children and adolescents is less common than in adults. Mutation in BRAF relates significantly to distant metastasis among children/adolescents with PTC.

Effects of different surgical approaches on health-related quality of life in pediatric and adolescent patients with papillary thyroid carcinoma

“…The annual incidence of thyroid cancer in children and adolescents is modest, with one to three cases per one million children [ 1 ]. Thyroid cancer is the leading cause of endocrine malignancies in children and adolescents, and its incidence is increasing [ 2 ]. The prognosis for thyroid cancer in children and adolescents is favorable, especially for papillary carcinoma [ 3 ].…”

An individualized protein-based prognostic model to stratify pediatric patients with papillary thyroid carcinoma

“…To date, the studies on the molecular mechanism of PPTC have been mostly limited to the genetic level [4][5][6][7] . They mainly focused on analyzing the PPTC etiology and providing a benign versus malignant diagnosis but did not produce tools for a personalized prognosis evaluation.…”

Evolving Aspects of Prognostic Factors for Pediatric Cancer

“…Mutated proto-oncogene B-Raf (BRAF) is the most common genetic alteration in adult PTC, and its prognostic significance has been extensively explored in adults [9]. Kotanidou et al conducted the first systematic review and meta-analysis on the prognostic significance of BRAF gene mutational status in children and adolescents [10]. Since immunomodulation with BRAF inhibitors and molecularly targeted therapy is an appealing contemporary approach, conclusions made from this systematic review may serve as useful tools to establish guidelines in children and adolescent patients with PTC.…”