The Association Between BRAF^V600E Mutation And Lymph Node Metastasis Of Papillary Thyroid Cancer And Its Effect On Stimulated Thyroglobulin After Radioactive Iodine

Background and ObjectivePapillary thyroid cancer(PTC)is the most common thyroid malignant tumor,accounting for more than 85%of thyroid cancer.Relevant literatures confirmed that V-raf murine sarcoma viral oncogene homolog B1(BRAF)V600E initiated the occurrence of PTC and was the most common genetic mutation in PTC.Although PTC patients generally have a good prognosis after standardized initial treatment,about 15%?20%of PTC patients could occur recureence or metastasis,mainly lymph node metastasis(LNM)recuenrrence.It has been reported that BRAFV600E mutation was closely related to the aggressive clinical characteristics of PTC,such as LNM.However,some studies showed the opposite.Radioactive iodine(RAI)is an effective treatment for PTC patients,but BRAFV600E mutation may affect the iodine uptake ability and clinical prognosis.Postoperative thyroglobulin(Tg)has been proved to be a specific tumor maker of differentiated thyroid cancer,and to some extent,Tg level can reflect the condition of PTC patients,and help determine the prognosis.After repeated RAI,PTC patients with BRAFV600E mutation may develope radioactive iodine refractory(RAIR).Yet there were limited studies on the trend of BRAFV600E mutation on stimulating thyroglobulin(s-Tg)after RAI treatment.Therefore,the study explored the association between BRAFV600E mutation and LNM of PTC and evaluated the clinical effect of BRAFV600E mutation on RAI by detecting the level of s-Tg and its change tendency in PTC patients who received at least two RAI treatments,aimed to provide the scientific basis of molecular foundation for the subsequent decision of clinical treatment scheme and out-patient follow-up strategy of PTC patients.METHODSDuring January 2013 to December 2018,a total of 3916 patients detected BRAFV600E mutation examination in our hospital.Clinicopathological data of 2647 PTC patients(male:599 and female:2048)who underwent total or near total thyroidectomy with central lymph node dissection and the postprerative pathology confirmed PTC were collected and analyzed retrospectively.According to the presence of the BRAFV600E,the patients were divided into BRAFV600E mutation group(2230 cases)and BRAFV600E wild group(417 cases).The differences of age,gender,tumor size and lymph node metastasis(LNM)between two groups was analyzed.86 patients(male:28 and female:58)who had received at least two RAI treatments was filtered and evaluated further in the differences of s-Tg level.RESULTS1.Difference in LNM between the BRAFV600E mutation group and the wild groupOverall prevalence of BRAFV600E mutation was 84.25%(2230/2647)in our study.There was no difference in gender,age or tumor size in PTC patients between two groups(P>0.05).However,BRAFV600E was associated with LNM of PTC patients(P<0.05),the proportion of LNM(48.39%vs 41.97%,P=0.016)in BRAFV600E mutation group was significantly higher than that in wild group.2.Difference in s-Tg and change trend after the first RAI between the BRAFV600E mutation group and the wild groupBefore the first RAI treatment,there was no significant difference in s-Tg level between groups(P>0.05);while after RAI treatment,s-Tg level of BRAFV600E mutation group was significantly higher than that of the wild group(61.16ng/ml vs 18.56ng/ml,P=0.003).Compared with the BRAFV600E mutation group,the level of s-Tg in wild group sharply decreased(P=0.006).CONCLUSION1.The presence of BRAFV600E mutation in PTC patients in our study was 84.25%.2.PTC patients with BRAFV600E mutation had a higher risk of LNM.3.Compared with BRAFV600E mutation group,s-Tg level was lower in the wild group after the first RAI and decreased sharply.4.BRAFV600E mutation may predict a worse clinical prognosis in PTC patients.