BRAF mutation in papillary thyroid cancer-Prevalence and clinical correlation in a South-East Asian cohort.

OBJECTIVE: BRAF mutation is the commonest mutation seen in papillary thyroid cancer (PTC), but its prevalence and clinical significance vary across countries. We aim to evaluate the prevalence and clinico-pathological correlation of BRAF mutation in PTC patients at our centre. STUDY DESIGN: Retrospective cohort study of 75 consecutive archival thyroid specimens, whereby BRAF mutation was detected using a polymerase chain reaction (PCR) technique and correlated with clinical and pathological features and outcomes. SETTING: Tertiary university hospital in Singapore. PARTICIPANTS: A total of 75 consecutive histologically proven archival thyroid specimens from patients who underwent thyroidectomy for PTC were accrued for this study. MAIN OUTCOME MEASURES: Main outcome is to determine the prevalence of the BRAF mutation in our South-East Asian population. Secondary aim is to correlate the mutational status with adverse pathological features like histological variants, multi-focality, lymphovascular invasion and extra-thyroidal extension, clinical features like demographics, TNM stage, recurrence and survival, as well as treatment details like type of surgery performed and radioiodine doses. RESULTS: BRAF mutation was detected in 56% (42/75) of PTC. All but one BRAF-mutated PTC had the BRAFV600E mutation. BRAF-mutated tumours were associated with an advanced T-stage (P = 0.049) and were more likely to have a central neck dissection (P = 0.036). There was no significant correlation between BRAF mutation status and clinical outcomes. CONCLUSION: The prevalence of BRAF mutation is 56%. BRAF mutation-positive tumours were associated with locally advanced disease, but not poorer survival.

Role of pfmdr1 mutations on chloroquine resistance in Plasmodium falciparum isolates with pfcrt K76T from Papua New Guinea.

The N86Y mutation in pfmdr1 is reported to play an additional role for the chloroquine resistance in Plasmodium falciparum isolates. However, not much has been done to clarify whether this mutation augments the level of chloroquine resistance in the isolates harboring pfcrt K76T mutation. We compared the in vitro chloroquine efficacy between pfcrt K76T mutant parasites with or without N86Y mutation from Papua New Guinea. A total of 57 isolates (4% sensitive, 14% borderline, and 82% resistant) were successfully tested in vitro for chloroquine sensitivity. We found a slightly higher effective concentration of chloroquine needed to inhibit P. falciparum by 50% (mean EC50=107 nM) in isolates with the pfcrt K76T+pfmdr1 N86Y than that in isolates with the pfcrt K76T+pfmdr1 N86 (EC50=88 nM), but this difference was not statistically significant. A significant non-random association was observed between the pfcrt K76T and pfmdr1 N86Y alleles. Our results suggest that the pfmdr1 N86Y mutation plays a compensatory role to chloroquine-resistant isolates under a chloroquine pressure while it may also augment the level of chloroquine resistance in the K76T parasites to a small extent.