Prevalence, risk factors, and BRAF mutation of colorectal sessile serrated lesions among Vietnamese patients

BACKGROUND Sessile serrated lesions(SSLs)are considered precancerous colorectal lesions that should be detected and removed to prevent colorectal cancer.Previous studies in Vietnam mainly investigated the adenoma pathway,with limited data on the serrated pathway.AIM To evaluate the prevalence,risk factors,and BRAF mutations of SSLs in the Vietnamese population.METHODS This is a cross-sectional study conducted on patients with lower gastrointestinal symptoms who underwent colonoscopy at a tertiary hospital in Vietnam.SSLs were diagnosed on histopathology according to the 2019 World Health Organi-zation classification.BRAF mutation analysis was performed using the Sanger DNA sequencing method.The multivariate logistic regression model was used to determine SSL-associated factors.RESULTS There were 2489 patients,with a mean age of 52.1±13.1 and a female-to-male ratio of 1:1.1.The prevalence of SSLs was 4.2%[95%confidence interval(CI):3.5-5.1].In the multivariate analysis,factors significantly associated with SSLs were age≥40[odds ratio(OR):3.303;95%CI:1.607-6.790],male sex(OR:2.032;95%CI:1.204-3.429),diabetes mellitus(OR:2.721;95%CI:1.551-4.772),and hypertension(OR:1.650,95%CI:1.045-2.605).The rate of BRAF mutations in SSLs was 35.5%.CONCLUSION The prevalence of SSLs was 4.2%.BRAF mutations were present in one-third of SSLs.Significant risk factors for SSLs included age≥40,male sex,diabetes mellitus,and hypertension.

Clinicopathological Features and Prognostic Value of KRAS/NRAS/BRAF Mutations in Colorectal Cancer Patients of Central China

The incidence of colorectal cancer(CRC)is increasing in China,with high mortality.Here,we aimed to evaluate the latest clinicopathological features and prognostic value of the KRAS/NRAS/BRAF mutation status in CRC patients in Central China.The clinical data of 1549 CRC patients with stage I-IV disease diagnosed at Union Hospital,Tongji Medical College of Huazhong University of Science and Technology from 2015 to 2017 were collected and analyzed retrospectively.KRAS/NRAS/BRAF mutations were detected by real-time quantitative polymerase chain reaction(q-PCR)in 410 CRC patients,with mutation frequencies of KRAS,NRAS and BRAF of 47.56%,2.93%and 4.15%,respectively.The gene mutation status and clinicopathological characteristics of 410 patients with CRC who underwent qPCR were analyzed.The KRAS and BRAF gene mutations were related to the pathological differentiation and number of metastatic lymph nodes.The BRAF gene mutation was also associated with cancer thrombosis in blood vessels.Cox regression analysis showed that there was no statistically significant difference in the overall survival(OS)between patients with KRAS,NRAS mutants and wild-type CRC patients,while the BRAF gene mutation was negatively correlated with the OS rate of CRC patients.It is suggested that the BRAF gene mutation may be an independent risk factor for the prognosis of CRC.

Contemporary treatment approaches for metastatic colorectal cancer driven by BRAF V600 mutations

The treatment of metastatic colorectal cancer(mCRC)harboring BRAF V600 mutations is challenging.These tumors are often refractory to standard treatment.Therefore,the patients may exhibit rapid clinical deterioration,depriving them of the chance to receive salvage therapy.In newly diagnosed patients with good performance status,the administration of an intensive chemotherapy regimen like FOLFOXIRI(5-fluorouracil,leucovorin,oxaliplatin,and irinotecan)along with the antiangiogenic agent bevacizumab can modify this aggressive behavior of the disease and improve patient clinical outcomes.The recently published results of the BEACON(Binimetinib,Encorafenib,and Cetuximab Combined to Treat BRAF-Mutant Colorectal Cancer)study demonstrated that a combination therapy consisting of BRAF,epidermal growth factor receptor,and mitogen-activated protein kinase kinase inhibitors could be a useful second-or third-line alternative.This review summarizes the current treatment strategies for BRAF-mutant mCRC.

BRAF mutation in multiple primary cancer with colorectal cancer and stomach cancer

Aims:Recently,BRAF mutation testing has been introduced as a marker in differentiating Lynch syndrome from sporadic colorectal cancers or in predicting colorectal cancers with worse prognosis.Individuals with hereditary predisposition to cancer development are at an increased risk of developing multiple primary cancers.The purpose of this study is to identify mutation in the BRAF gene in multiple primary cancers with colorectal cancer and stomach cancer.Methods:BRAF mutation was analysed in 45 patients with colorectal cancer and stomach cancer,synchronously or metachronously.Results:Mean age was 64.07 years(range:47–83 years).For the colorectal cancer,tumors were located at the sigmoid colon in eight patients(17.8%)and at the rectum in 22 patients(48.9%).Twenty-three patients(51.1%)had synchronous cancer.Four patients(8.9%)had family members with cancer.BRAF mutation was identified in three patients(6.7%).All three of these patients had metachronous cancers.The colorectal cancers were located in the sigmoid colon(1 patient)and the rectum(2 patients).Conclusions:BRAF mutation rate was low in the multiple primary cancer with colorectal cancer and stomach cancer.With only BRAF gene study,it was not possible to identify any correlation with family history of colorectal cancer.Further study means considering other genes–MSI,MSH2,MLH1,MSH6.

Different effects of the inhibition of Src activity on Akt/PKB in melanoma cells with wild BRAF and mutated BRAF V600E

Src regulates cell adhesion, invasiveness, motility and growth in cancer cells. In melanoma, accumulating data show that Src inhibition can be effective and may enhance the effects of other agents. Increased Src expression and activity thus has recently become a target for drug therapy. Several melanoma cell lines were exposed to inhibitors of Src activity despite their broad specificity. To examine the particular activity of Src in human melanoma cells, we used SU6656, the selective inhibitor of Src family protein kinases. The activity of Src and cell proliferation were suppressed in HBL human cells, wild type melanoma cells and in SK-MEL-5 human melanoma cells harboring mutant BRAF V600E, upon their treatment with SU6656. The suppression of Src kinase activity had not inhibitory effects on Akt/PKB activity in SK-MEL-5 cells, which we have previously found in HBL cells. This may indicate that changes of Src involvement in the control of Akt/PKB activity and its downstream signaling could be induced by BRAF V600E mutation in SK-MEL-5 cells.

Clinicopathologic Characteristics of Differentiated Thyroid Carcinoma in Children and Adolescents

Objective: To investigate the clinicopathologic features of differentiated thyroid carcinoma in children and adolescents. Methods: The clinical data of 7 children and adolescents with differentiated thyroid carcinoma were retrospectively analyzed, and the clinicopathologic features of differentiated thyroid carcinoma were analyzed by gender, tumor size and BRAF mutation. Results: There were 7 cases of thyroid papillary carcinoma. The mean age of patients was (18.71 ± 2.75), and the mean tumor diameter was (2.4 ± 1.04) cm. Lymph node metastasis rate was 100% (7/7). In children and adolescents, the lesion volume was larger, membrane invasion and vascular cancer thrombus were more likely to occur, BRAF mutation was less common, and the difference was statistically significant. Conclusion: Children and adolescents with differentiated thyroid carcinoma are more aggressive and prone to membrane invasion and lymph node metastasis;BRAF mutation is less common than in adults.

Skeletal muscle metastasis with bone metaplasia from colon cancer:A case report and review of the literature

BACKGROUND Colon cancer is a common malignant disease of the gastrointestinal tract and usually occurs at the junction of the rectum and sigmoid colon.Lymphatic and hematogenous metastases occur frequently in colon cancer and the most common metastatic sites include the liver,lung,peritoneum,bone,and lymph nodes.As a manifestation of advanced tumor spread and metastasis,soft tissue metastasis,especially skeletal muscle metastasis with bone metaplasia caused by colon cancer,is rare,accounting for less than 1%of metastases.CASE SUMMARY A 43-year-old male patient developed skeletal muscle metastasis with bone metaplasia of the right proximal thigh 5 mo after colon cancer was diagnosed.The patient was admitted to the hospital because of pain caused by a local mass on his right thigh.Positron emission tomography-computed tomography showed many enlarged lymph nodes around the abdominal aorta but no signs of lung or liver metastases.Color ultrasound revealed a mass located in the skeletal muscle and the results of histological biopsy revealed a poorly differentiated adenocarcinoma suspected to be distant metastases from colon cancer.Immunohistochemistry showed small woven bone components that were considered to be ossified.CONCLUSION This case reminds us that for patients with advanced colorectal tumors,we should be alert to the possibility of unconventional metastasis.

BRAF和KRAS突变型转移性结直肠癌:个体化治疗的前景

结直肠癌是世界上最常见的恶性肿瘤之一,30%的结直肠癌伴有转移。转移性结直肠癌(mCRC)患者5年总生存率不足10%。临床研究显示,抗EGFR药物用于mCRC的一线化疗,疗效有限,因此,许多研究聚焦到了BRAF和KRAS突变。过去对于转移性结直肠癌患者的治疗,并不考虑BRAF或KRAS突变与否。但后来在临床研究中发现,这两种基因突变的mCRC患者预后极差,因此,有必要筛选出BRAF或KRAS突变的mCRC患者,制定合理的治疗策略,以改善其预后和生存。mCRC患者BRAF和KRAS突变率大概分别为10%和44%。尽管mCRC患者整体生存近年来有所改善,但伴有这两种基因突变的患者对治疗的反应及预后仍然很差。因此,亟需制定出针对BRAF或KRAS突变型mCRC的前瞻性个体化治疗策略。本文中,我们重点关注mCRC患者的BRAF和KRAS突变,以了解其耐药机制,思考如何提高这些突变患者的治疗反应、临床疗效及远期预后,并探讨了BRAF和KRAS突变型mCRC的前瞻性个性化治疗策略。