ABSTRACT
BACKGROUND: The BRAF (V600E) mutation is a recognised molecular marker in papillary thyroid cancer (PTC), reported incidence from 30 to 80 %. BRAF(V600E) aberrantly activates the MAPK pathway, a central regulator of cell growth and proliferation. Previous studies have reported conflicting data regarding the impact of BRAF(V600E) on clinicopathological features of PTC. The study aims to determine whether BRAF(V600E) is useful as a prognostic biomarker in PTC. METHODS: A cohort study of patients undergoing surgery for PTC was undertaken. The primary outcome measure was disease-free survival. Secondary outcome measures were tumour size, nodal positivity and radioactive iodine ablation rate. All cases were re-examined to confirm PTC. Immunohistochemistry for BRAF(V600E) was performed on tissue microarrays. A single endocrine pathologist, blinded to clinicopathological data, interpreted staining. RESULTS: 496 patients with PTC were included, and 309 (62 %) were BRAF(V600E) positive. Tumour size was similar for BRAF(V600E)-positive and -negative tumours (21.3 vs. 23.2 mm, p = 0.23). BRAF(V600E)-positive patients were significantly older at first operation (mean age 45 versus 49 years, p = 0.003). BRAF(V600E)-positive PTCs had a higher rate of disease recurrence (12.9 vs. 5.6 %, p = 0.004), lymph node metastasis (44 vs. 29.4 %, p = 0.004) and extra-thyroidal extension (44 vs. 22 %, p < 0.001). Five-year disease-free survival was 89.6 % for BRAF(V600E) positive and 96.3 % for negative tumours, p < 0.001. There was no difference between groups for vascular invasion or multifocality. The mean follow-up was 57 months for both groups. CONCLUSION: BRAF(V600E) in PTC predicts an increased risk of lymph node metastasis, extra-thyroidal extension and reduced disease-free survival. It is an additional useful prognostic biomarker.
Subject(s)
Carcinoma/genetics , Carcinoma/secondary , Neoplasm Recurrence, Local/genetics , Proto-Oncogene Proteins B-raf/genetics , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathology , Ablation Techniques , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Carcinoma/surgery , Carcinoma, Papillary , Child , Cohort Studies , Disease-Free Survival , Female , Humans , Iodine Radioisotopes/therapeutic use , Lymphatic Metastasis , Male , Middle Aged , Mutation , Proto-Oncogene Proteins B-raf/analysis , Thyroid Cancer, Papillary , Thyroid Neoplasms/surgery , Tumor Burden/genetics , Young AdultABSTRACT
The effect of spray drying conditions on the chemical composition of Brazilian green propolis extract was investigated using a factorial design and high performance liquid chromatography. The raw and dried extract contents of caffeic acid, p-coumaric acid, drupanin, isosakuranetin, artepillin C, baccharin and 2,2-dimethyl-6-carboxyethenyl-2H-1-benzopyran were quantified using veratraldehyde (3,4-dimethoxybenzaldehyde) as internal standard. The baccharin content in spray-dried propolis was affected by the drying temperature with a 5% significance level, while the coumaric acid and drupanin contents were dependent on drying temperature at a 15% significance level. The other chemical markers, caffeic acid, isosakuranetin, artepillin C and 2,2-dimethyl-6-carboxyethenyl-2H-1-benzopyran, showed to be independent of drying conditions. However, all the chemical markers showed some loss on drying, which varied from 30 to 50%. The results showed that prenylated compounds are sensitive to drying, but their losses may be considerably reduced under low temperatures, around 40 degrees C. The antioxidant activity of the spray dried propolis was determined by the diphenylpicrylhydrazyl (DPPH) method and showed a quadratic dependency on the temperature; extract feed rate and the interaction between them. However, spray dried propolis extracts presented antioxidant activities similar to the original propolis tincturae.
