title: Is BRAFV600E mutation a marker for central nodal metastasis in small papillary thyroid carcinoma?
abstract: Utilizing BRAF(V600E) mutation as a marker may reduce unnecessary prophylactic central neck dissection (pCND) in clinically nodal negative (cN0) neck for small (≤2 cm) classical papillary thyroid carcinoma (PTC). We aimed to assess whether BRAF is a significant independent predictor of occult central nodal metastasis (CNM) and its contribution to the overall prediction after adjusting for other significant preoperative clinical factors in small PTC. Primary tumor tissue (paraffin-embedded) from 845 patients with small classical cN0 PTC who underwent pCND was tested for BRAF mutation. Clinicopathologic factors were compared between those with and without BRAF. BRAF was evaluated to see if it was an independent factor for CNM. Prediction scores were generated using logistic regression models and their predictability was measured by the area under the ROC curve (AUC). The prevalence of BRAF was 628/845 (74.3%) while the rate of CNM was 285/845 (33.7%). Male sex (odds ratio (OR): 2.68, 95% CI: 1.71-4.20), large tumor size (OR: 2.68, 95% CI: 1.80-4.00), multifocality (OR: 1.49, 95% CI: 1.07-2.09), lymphovascular permeation (OR: 10.40, 95% CI: 5.18-20.88), and BRAF (OR: 1.65, 95% CI: 1.10-2.46) were significant independent predictors of CNM, while coexisting Hashimoto's thyroiditis (OR: 0.56, 95% CI: 0.40-0.80) was an independent protective factor. The AUC for prediction score based on tumor size and male sex was similar to that of prediction score based on tumor size, male sex, and BRAF status (0.68 vs 0.69, P=0.60). Although BRAF was an independent predictor of CNM, knowing its status did not substantially improve the overall prediction. A simpler prediction score based on male sex and tumor size might be sufficient.
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong SAR, China Department of Surgery, Seoul National University College of Medicine and Hospital, Seoul, Korea School of Public Health, The University of Hong Kong, Hong Kong SAR, China Department of Pathology, Seoul National University College of Medicine and Hospital, Seoul, Korea Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Brian Hung-Hin
authors.initials: BH
authors.lastname: Lang
authors.forename: Young Jun
authors.initials: YJ
authors.lastname: Chai
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Cowling
authors.forename: Hye Sook
authors.initials: HS
authors.lastname: Min
authors.forename: Kyu Eun
authors.initials: KE
authors.lastname: Lee
authors.forename: Yeo-Kyu
authors.initials: YK
authors.lastname: Youn
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002291:Carcinoma, Papillary; D002648:Child; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D047368:Tumor Burden; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF mutation; central neck dissection; hypoparathyroidism; papillary thyroid carcinoma; recurrent laryngeal nerve