Advances in treatment of metastatic colorectal cancer with BRAF gene mutation / 中国综合临床

Objective V-raf murine sarcoma virus oncogene homologous gene B (BRAF) gene plays an important role in mitogen-activated protein kinase signaling pathway by encoding RAF family serine/ threonine protein kinase.Mutations in the BRAF gene can lead to tumorigenesis.About 10％ of metastatic colorectal cancers have BRAF gene mutations.The prognosis of this type of cancer is poor,with a median overall survival of 12 months.Recent studies have shown that FOLFOXIRI regimen combined with bevacizumab can be used as a first-line treatment.In addition,simultaneous targeting inhibition of multiple signaling pathways can bring survival benefits to these patients.

Clinical pathological characteristics of resectable papillary thyroid microcarcinoma / 中华肿瘤杂志

Objective@#To investigate the difference of prognostic factors and recurrence rates between papillary thyroid microcarcinoma (PTMC) and lager papillary thyroid carcinoma (PTC) and analyze the clinical pathological characteristics of PTMC suitable for surgery.@*Methods@#A retrospective analysis on the clinicopathological features, expression level of of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E gene mutation and pigment epithelium-derived factor (PEDF), and postoperative follow-up results of the 251 PTC patients who underwent surgical treatment from October 2011 to October 2013, including 169 cases with PTMC and 82 with lager PTC (Tumor diameter>1 cm).@*Results@#The BRAF V600E mutation rates of PTMC and lager PTC patients are 65.1%(110/169)and 78.0% (64/82) respectively, and the difference is statistically significant (P<0.05). The prevalence of extrathyroidal invasion (7.1%) and lymph nodes metastasis (27.2%) of the patients with PTMC were significantly lower than those of the patients with larger PTC (15.9% and 46.3%, respectively)(P<0.01). The follow-up durations for PTMC and lager PTC were (45.6±3.6) months and (45.0±3.4) months, respectively (P>0.05). There was no statistic significance for the difference in age, gender, coexistent hashimoto′s thyroiditis, PEDF expression, and recurrence rate between the patients with PTMC and with larger PTC (P>0.05). The recurrence rate of the patients who have the high risk factors of PTMC was 1.6%(2/122)and that of larger PTC was 4.9% (4/82).@*Conclusions@#Extrathyroid invasion, lymph node metastases and BRAF V600E gene mutation are the high risk factors of recurrent PTMC. The same treatment strategy should be considered for PTMC with coexistent high risk factors as that for larger PTC. For PTMC with BRAF V600E gene mutation, earlier surgical treatment is suggested. PTMC patients with BRAF V600E gene mutation and high cell subtype are suggested to undergo total thyroidectomy for the first operation in order to reduce the potential risk of recurrence.

Thyroid cytological examination by using fine needle aspiration biopsy combined with BRAF gene testing: its diagnostic value in differentiating benign from malignant thyroid nodules / 介入放射学杂志

Objective To evaluate the combination use of thyroid fine needle aspiration biopsy (FNAB)and V-Raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E gene mutation testing in differentiating benign from malignant thyroid nodules.Methods A total of 64 patients with pathologically-proved thyroid nodules were included in this study.The clinical data,including preoperative ultrasound-guided thyroid FNAB and BRAF V600E gene mutation detection,were retrospectively analyzed.Taking postoperative histopathological results as diagnostic gold standard for the thyroid nodule,the diagnostic values of simple FNAB,simple BRAF V600E gene mutation testing,and combination use of FNAB and BRAF V600E gene mutation detection were separately assessed.Results In the 62 patients a total of 64 nodules were detected (2 patients having bilateral nodules) and treated with surgery.Of the 64 nodules,BRAF V600E mutation was detected in 44 nodules,and 43 nodules were proved to be thyroid papillary carcinoma by postoperative pathological examination.Among the 44 nodules showing BRAF V600E mutation,FNAB made malignant diagnosis in 28,benign diagnosis in 6,and uncertain diagnosis in 10.Of the 20 nodules showing no BRAF V600E mutation,FNAB made malignant diagnosis in 5,benign diagnosis in 3,and uncertain diagnosis in 12.The postoperative pathological examination confirmed that 14 lesions were thyroid papillary carcinoma,4lesions were nodular goiter,one lesion was subacute thyroiditis,and one lesion was thyroid adenoma.Among the 57 thyroid papillary carcinomas,BRAF V600E mutation was detected in 43,with the mutation rate being 75.4％.Compared with the gold standard based on pathological diagnosis,the sensitivity,specificity,positive predictive value,negative predictive value,correct diagnosis rate of FNAB for judging benign or malignant thyroid nodules were 78.9％,85.7％,97.8％,33.3％ and 79.7％ respectively,which of BRAF V600E gene mutation detection for judging benign or malignant thyroid nodules were 75.4％,85.7％,97.7％,30.0％ and 76.6％ respectively,and which of FNAB plus BRAF V600E gene mutation detection for judging benign or malignant thyroid nodules were 94.7％,71.4％,96.4％,62.5％ and 92.2％ respectively.By using McNemar paired data x2 test to compare FNAB with combination use of FNAB plus BRAF V600E gene mutation detection in diagnosing thyroid nodules,the results indicated that statistically significant deference in differentiating benign from malignant thyroid nodules existed between the two methods (P＜0.001).Conclusion For the qualitative diagnosis of thyroid nodules which nature cannot be determined by simple FNAB,FNAB combined with BRAF V600E gene mutation detection can improve the diagnostic accuracy for benign and malignant thyroid nodules.

A Case of Cardiofaciocutaneous Syndrome caused by BRAF gene mutation

Cardiofaciocutaneous (CFC) syndrome is characterized by dysmorphic features, cardiac anomalies, and cutaneous abnormalities. CFC syndrome belongs to the class of Noonan-related diseases. CFC syndrome can be clinically differentiated from other Noonan-related diseases by the distinct craniofacial features of sparse hair, a hypoplastic supraorbital ridge, exophthalmos and nystagmus, and skin manifestations such as ichthyosis and hyperkeratosis. However, phenotypes can overlap among Noonan-related syndromes, including CFC syndrome. Recently, several genes in the RAS-MAPK pathway have been identified as disease-causing genes for Noonan-related diseases. Here, we report on a Korean girl diagnosed with CFC syndrome caused by a V-raf murine sarcoma viral oncogene homolog B1 (BRAF) gene mutation, and we discuss the phenotype-genotype heterogeneities in Noonan syndrome and Noonan-related diseases.