BRAF V600E mutation and its association with clinicopathological features of papillary thyroid cancer: a meta-analysis.
BACKGROUND
There is conflicting literature regarding the association of the BRAF V600E mutation and aggressive clinicopathological features of papillary thyroid cancer (PTC). Nevertheless, some propose that BRAF status be incorporated into the management of patients with PTC, specifically recommendations regarding lymph node dissection. We therefore performed a meta-analysis to examine the relationship between BRAF and clinicopathological features of PTC.


METHODS
A literature search was performed within PubMed and EMBASE databases using the following Medical Subject Headings (MeSH) and keywords: "braf," "mutation," "thyroid," "neoplasm(s)," "tumor," "cancer," and "carcinoma." Individual study-specific odds ratios and confidence intervals were calculated, as were Mantel-Haenszel pooled odds ratios for the combined studies.


RESULTS
Thirty-two studies including 6372 patients were reviewed. BRAF mutation was associated with lymph node metastases (LNM), advanced stage, extrathyroidal extension, tumor size, male gender, multifocality, absence of capsule, classic PTC, and tall-cell variant PTC. There was no association with age or vascular invasion. Only two studies were prospective; nine included consecutive patients, whereas one included randomly selected patients; and only two included patients who had undergone routine central lymph node dissection and were thus evaluable for the presence of LNM.


CONCLUSIONS
Meta-analysis found that BRAF mutation is associated with LNM, stage, extrathyroidal extension, tumor size, male gender, multifocality, absence of capsule, classic PTC, and tall-cell variant PTC in PTC. However, almost all studies were retrospective and only two of 32 included patients who had undergone routine central lymph node dissection, emphasizing the need for well-designed studies to appropriately examine this association before making important clinical decisions.
Endocrine Surgery Section, Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
Carol
C
Li
Kathleen C
KC
Lee
Eric B
EB
Schneider
Martha A
MA
Zeiger
D000367:Age Factors; D019943:Amino Acid Substitution / Q000235:genetics / Q000502:physiology; D002277:Carcinoma / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D002291:Carcinoma, Papillary; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D018698:Glutamic Acid / Q000235:genetics; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D020125:Mutation, Missense / Q000502:physiology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012727:Sex Characteristics; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D047368:Tumor Burden; D014633:Valine / Q000235:genetics
D018698:Glutamic Acid; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D014633:Valine