ObjectiveTo investigate research advance on the value of B-type RAF kinase (BRAF) gene mutation assisted diagnosis of papillary thyroid cancer (PTC) in thyroid nodule.MethodThe recent literatures on the BRAF gene mutation and its combination with fine needle aspiration cytology (FNAC) in the diagnosis of benign and malignant thyroid nodules and PTC were collected and reviewed.ResultsThe BRAFV600E gene mutation was the most common type of gene mutation in the genetic molecule of PTC. The combination of the FNAC and BRAF gene mutation detection could improve the diagnostic value of the benign and malignant thyroid nodules, especially the diagnostic accuracy of PTC. However, the negative detection of BRAF gene mutation did not rule out the possibility of PTC. It still remained controversial that the detection of BRAF gene mutation could differentiate between the benign and malignant thyroid nodules.ConclusionsBRAF gene mutation detection has different diagnostic values in different types of thyroid nodules. It has considerable diagnostic value in thyroid nodules with high BRAF mutation incidence (suspicious for malignancy, undetermined significance or follicular lesion of undetermined significance nodules) while presents false negative result in thyroid nodule with very low mutation incidence category to a large extent. BRAF gene detection might become a specific diagnostic molecular marker to promote diagnosis accuracy of PTC.
ObjectiveTo study the expressions of BRAF gene in papillary thyroid microcarcinoma (PTMC) and papillary thyroid carcinoma (PTC) >1 cm in diameter, and the invasiveness of PTMC and PTC. MethodsThe data of 275 patients with PTC received surgical treatment and with BRAF gene mutation results in West China Hospital of Sichuan University from 2011 September to 2013 September were retrospectively analyzed. According to the size of tumors, the patients were divided into three groups, was the diameter <1 cm group, 1 cm< diameter≤2 cm group, and diameter >2 cm group,respectively. The ratio of BRAF gene mutation, and the degree of risk of extrathyroidal invasion and lymph node metastasis were compared. ResultsUnivariate analysis showed that tumor size was not related with the age, gender, and BRAF gene mutation rate (P>0.05), while the tumor size was related with the extrathyroidal invasion and lymph node metastasis (P<0.05), and the ratio of BRAF gene mutation was related with the extrathyroidal invasion and lymph node metastasis (P<0.05). Multivariate analysis showed that tumor size was associated with extrathyroidal extension (P=0.009) and lymph node metastasis (P=0.000). ConclusionsBRAF gene mutation can increase the extrathyroidal invasion and lymph node metastasis risk of PTC, and it is no significantly correlated with tumor size of PTC. The invasiveness of PTC increases with the increased of tumor size, but the PTMC of BRAF gene mutation positive is still require positive treatment.
ObjectiveTo investigate the correlation between different RAS/BRAF mutation sites and the clinicopathological characteristics, metastatic sites, and prognosis of patients with colorectal cancer. MethodsA retrospective analysis was conducted on the clinicopathological data of 415 patients with stage Ⅰ –Ⅲ microsatellite stability (MSS) colorectal cancer who underwent radical surgery at the Department of Colorectal Surgery, The First Affiliated Hospital of Zhejiang University, and the Department of General Surgery, Gansu Provincial People’s Hospital, from March 1, 2017, to October 1, 2022, and had next-generation sequencing data. According to the presence and sites of RAS/BRAF mutations, patients were divided into five groups: RAS/BRAF wild-type group, KRAS G12 codon mutation group, KRAS G13 codon mutation group, BRAFV600E mutation group, and other RAS codon mutation group. The clinicopathological characteristics and prognostic differences between the four groups of RAS/BRAF mutant colorectal cancer patients and the RAS/BRAF wild-type colorectal cancer patients were compared. ResultsAmong stage Ⅰ –Ⅲ MSS colorectal cancer patients, there were 166 cases (40.0%) of wild-type RAS/BRAF without mutation, 124 cases (29.9%) of KRAS G12 mutation, 55 cases (13.3%) of KRAS G13 mutation, 23 cases (5.5%) of BRAFV600E mutation, and 47 cases (11.3%) of other RAS codon mutations. Clinicopathological characteristics analysis revealed that BRAFV600E mutation was associated with mucinous adenocarcinoma (P=0.033). Compared with the wild-type group, KRAS G12 mutation could increase the probability of metachronous lung metastasis (P=0.003) and reduce the probability of metachronous liver metastasis (P=0.013); the KRAS G13 mutation and other RAS mutations could increase the probability of metachronous lung metastasis (P=0.004, P=0.006). Univariate and multivariate Cox proportional hazards regression analysis showed that among the RAS/BRAF codon mutations, only KRAS G13 mutation was an independent prognostic factor for poor prognosis in stage Ⅰ –Ⅲ colorectal cancer. ConclusionsDifferent RAS/BRAF gene codon mutations are associated with distinct clinicopathological characteristics and organ metastatic sites in colorectal cancer. KRAS G13 codon mutation is an independent prognostic factor for poor prognosis in stage Ⅰ –Ⅲ colorectal cancer. It is recommended that routine detection of RAS/BRAF gene site mutations should be performed in stage Ⅰ –Ⅲ colorectal cancer patients to guide the follow-up management and help clinicians make rational clinical decisions after tumor recurrence.
Objective To detective KRAS and BRAF mutations in gastrointestinal stromal tumors (GISTs) and explore its significance in resistance of imatinib treatment. Methods Three hundred and eighty-one c-kit/PDGFRA mutation samples, 119 c-kit/PDGFRA wild type samples, and 19 pairs of samples before and after imatinib resistance from 519 patients with GIST were enrolled in this study. Polymerase chain reaction was used to detect KRAS exon 2 and BRAF exon 15 mutations. The survival data were evaluated in patients with KRAS or BRAF mutation. Results KRAS mutation was found in 2 cases (1.7%) of c-kit /PDGFRA wild type GISTs, the type of KRAS mutation was G12D and G12C, respectively. BRAFV600E mutation was found in 2 cases (1.7%) of wild type GISTs. No KRAS and BRAF mutations were found in the patients with the c-kit/PDGFRA mutation GISTs and pairs of GISTs before and after imatinib resistance. Two patients with KRAS mutation showed shorter progression free survivals for imatinib treatment. Two patients with BRAF mutation had longer recurrence free survivals. Conclusions Low frequency of KRAS or BRAF mutation only happens in wild type GISTs. KRAS mutation might be related to imatinib primary resistance, but not to secondary resistance.
Objective To investigate the diagnostic significance of fine needle aspiration cytology (FNAC) combined with BRAFV600E gene detection in the diagnosis of cervical lymph node metastasis of thyroid cancer. Methods Atotal of 140 patients with suspected cervical lymph node metastasis of thyroid cancer were collected as the research objects, and all patients were given ultrasound-guided FNAC and detection of BRAFV600E gene. The significance of the diagnosis was analyzed according to the gold standard after pathological examination. Results All the 140 patients underwent surgical treatment. For FNAC, the sensitivity was 63.6% (84/132), the specificity was 100% (8/8), the accuracy was 65.7% (92/140), the positive predictive value was 100% (84/84), and the negative predictive value was 14.3% (8/56). For detection of BRAFV600E gene, the sensitivity was 84.8% (112/132), the specificity was 100% (8/8), the accuracy was 85.7% (120/140), the positive predictive value was 100% (112/112), and the negative predictive value was 28.5% (8/28). For FNAC combined with BRAFV600E gene detection, the sensitivity was 90.9% (120/132), the specificity was 100% (8/8), the accuracy was 91.4% (128/140), the positive predictive value was 100% (120/120), and the negative predictive value was 40.0% (8/20). The area under curve of receiver operating characteristic for FNAC, detection of BRAFV600E gene, and FNAC combined with BRAFV600E gene detection were 0.818, 0.924, and 0.955, respectively. Conclusion FNAC combine with BRAFV600E gene detection improves the accuracy of neck lymph node metastasis in patients with thyroid cancer, which is worthyof performed.
ObjectiveTo identify the risk factors of central lymph nodal (CLN) metastasis in papillary thyroid carcinoma (PTC) and indicate central neck dissection. MethodsFifty cases were analyzed retrospectively. The BRAFV600E gene mutation was analyzed by sequencing and expression of VEGF-C was analyzed by using immunohistochemically. The clinicopathologic and molecular marker factors relating to CLN metastasis were analyzed. ResultsThe BRAFV600E gene mutation was found in 30 of 50 (60.0%) patients of PTC. Univariate analysis showed that BRAFV600E gene mutation of PTC patients was significantly correlated with high expression of VEGF-C (87.5% vs. 34.6%,P=0.000), not with clinicopathologic factors. High expression of VEGF-C was significantly correlated with CLN metastasis in PTC (87.5% vs. 57.7%, P=0.019). Multivariate analysis showed that invasion of the surrounding tissues (P=0.009,OR=9.082,95% CI:1.748-47.185) and the high expression of VEGF-C (P=0.009,OR=9.082,95% CI:1.748-47.185) were independent risk factors for the presence of CLN metastases. Conclusions①The BRAFV600E gene mutation for PTC patients is significantly correlated with high expression of VEGF-C, not with CLN metastasis in PTC. ②High expression of VEGF-C is significantly correlated with CLN metastasis in PTC. ③Tumor extrathyroidal extension, especially invasion of the surrounding tissues is significantly correlated with CLN metastasis in PTC.
ObjectiveTo evaluate the frequency of BRAFV600E mutation and the association between BRAFV600Emutation and clinicopathologic characteristics of papillary thyroid carcinoma (PTC) in Chinese population by Meta-analysis. MethodsThe relevant published studies before January 2014 were reviewed according to the defined selection criteria using the PubMed,Embase,VIP,China Biology Medicine Database,Wanfang and China Knowledge Resource Integrated Database. The effect sizes of outcome parameters were estimated by odds ratio (OR) or weighted mean difference with a 95% confidence interval (CI). The quality of the included trials was assessed and Meta-analyses were conducted by RevMan 5.1 software. ResultsThe study included 46 studies with a total of 5 831 patients. The prevalence of BRAFV600E mutation ranged from 25% to 83%,with an overall prevalence of 54.6%. The clinicopathologic characteristics of 5 542 patients were analyzed. There were statistical significances in association between BRAFV600E mutation and the presence of classical type [OR=2.30,95%CI (1.32,4.01),P=0.003],follicular type [OR=0.44,95%CI (0.23,0.86),P=0.02],extrathyroidal extension [OR=2.18,95%CI (1.83,2.59),P<0.00001],multifocality [OR=1.31,95%CI (1.07,1.60),P=0.009],lymphocytic thyroiditis [OR=0.31,95%CI (0.23,0.42),P<0.00001],lymph node metastasis [OR=1.95,95%CI (1.40,2.72),P<0.000 1],advanced TNM stage [OR=2.41,95%CI (2.01,2.88),P<0.00001] and recurrence [OR=3.22,95%CI (2.04,5.09),P<0.00001],but the correlation of BRAFV600E mutation was not significant with gender,mean age,mean tumor size,age being ≥45 years,tumor size being ≥10 mm,tall cell type,and distant metastases (P>0.05). ConclusionIn Chinese patients,PTC with BRAFV600E mutation has more aggressive clinicopathologic characteristics than that without BRAFV600E mutation. The BRAFV600E mutation may be used as an important prognostic marker for patients with PTC.
ObjectiveTo investigate the relationship of concomitant BRAFV600E gene mutation with the predictive factors of papillay thyroid microcarcinoma(PTMC). MethodsBy fluorescence quantitative PCR method to detect BRAFV600E gene mutation of PTMC of 86 cases, and to detect the relationship with clinical pathological features of PTMC by single factor and multi-factor logistic regression analysis. ResultsThe morbidity of BRAFV600E gene mutation was 65.1%(56/86). By univariate analysis, BRAFV600E gene mutation status showed a related trend with lymph node metastasis(P=0.057). The multivariate analysis showwd that lymph node metastasis was correlated with BRAF V600E gene mutation(P < 0.05). When the diameter of tumor > 5 mm and≤10mm, BRAFV600E gene mutation was no statistically significantly related to central lymph node metastasis(P > 0.05). When BRAFV600E gene mutations was negative in patients with tumor diameter≤5 mm, no lymph node metastasis sample appeared. ConclusionsThe presence of BRAFV600E gene mutation is an independent predictive factor for central lymph node metastasis. When PTC with preoperative BRAFV600E gene mutation positive, the central neck dissection should be routine performed. There should be re-examined the necessity of preventative central lymph node disection when the tumor diameter is 5 mm or less with the patients which mutation negative.
This study reports a case of a 56-year-old female patient with BRAF-mutated non-small cell lung cancer (NSCLC) who successfully underwent curative surgery after neoadjuvant targeted therapy with the BRAF inhibitor dabrafenib combined with the MEK inhibitor trametinib. The chest drainage tube was removed 2 days postoperatively, and the patient was discharged smoothly. Postoperative pathology indicated invasive adenocarcinoma, moderately to highly differentiated, with 80% being lepidic type, and the maximum tumor diameter was 4 cm. No vascular invasion, nerve invasion, air cavity dissemination, pleural invasion, or lymph node metastasis were observed. The postoperative staging was ypT2aN0M0. The patient continued with adjuvant treatment with dabrafenib combined with trametinib postoperatively, and no signs of recurrence were found in the follow-up examination six months after surgery.
ObjectiveTo evaluate the diagnostic value of BRAFV600E mutation test in high-risk thyroid nodules with easily underdiagnosed fine-needle aspiration biopsy (FNAB) results.MethodsRetrospectively collected 122 cases of thyroid nodule who treated in the Hebei Petrochina Central Hospital between January 2017 and December 2018, all the cases admitted preoperative ultrasound and FNAB detection. All of the patients had the non-positive cytological results of FNAB and the high-risk features of ultrasound. Contrasted the postoperative pathological coincidence rate of combination of FNAB and BRAFV600E test with FNAB alone.ResultsThe BRAFV600E mutation rate was 27.0% (33/122). The positive rate of BRAFV600E mutation increased with the increase of ultrasound thyroid imaging reporting and data system(TI-RADS) grade (P<0.05), which was independent of patients’ age, gender, number of nodules, diameter of nodules, and FNAB results (P>0.05). The coincidence rate of FNAB combined with BRAFV600E mutation detection was higher than that of FNAB alone ［86.9% (106/122) vs. 69.7% (85/122), P<0.05).ConclusionsThe BRAFV600E mutation test can detect papillary thyroid carcinoma that might be missed by FNAB. We recommend that FNAB should be routinely accompanied by the BRAFV600E mutation test in the high-risk thyroid nodules.