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 path...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.展开更多
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 pat...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.展开更多
AIM: To investigate the prognostic role of KRAS and BRAF mutations after adjustment for microsatellite instability(MSI) status in Japanese colorectal cancer(CRC) population.METHODS: We assessed KRAS and BRAF mutations...AIM: To investigate the prognostic role of KRAS and BRAF mutations after adjustment for microsatellite instability(MSI) status in Japanese colorectal cancer(CRC) population.METHODS: We assessed KRAS and BRAF mutations and MSI status in 813 Japanese patients with curatively resected, stage Ⅰ-Ⅲ CRC and examined associations of these mutations with disease-free survival(DFS) and overall survival(OS) using uni- and multivariate Cox proportional hazards models.RESULTS: KRAS and BRAF mutations were detected in 312(38%) of 812 and 40(5%) of 811 tumors, respectively. KRAS mutations occurred more frequently in females than in males(P = 0.02), while the presence of BRAF mutations was significantly associated with the female gender(P = 0.006), proximal tumor location(P < 0.001), mucinous or poorly differentiated histology(P < 0.001), and MSI-high tumors(P < 0.001). After adjusting for relevant variables, including MSI status, KRAS mutations were associated with poorer DFS(HR = 1.35; 95%CI: 1.03-1.75) and OS(HR = 1.46; 95%CI: 1.09-1.97). BRAF mutations were poor prognostic factors for DFS(HR = 2.20; 95%CI: 1.19-4.06) and OS(HR = 2.30; 95%CI: 1.15-4.71). Neither the BRAF by MSI interaction test nor the KRAS by MSI interaction test yielded statistically significant results for DFS and OS.CONCLUSION: KRAS and BRAF mutations are associated with inferior survival, independent of MSI status, inJapanese patients with curatively resected CRC.展开更多
AIM:To identify and assess mutations in the K-ras and BRAF genes in a cohort of Chinese patients with colorectal cancer (CRC) for their association with various clinicopathological parameters and prognosis.METHODS:Gen...AIM:To identify and assess mutations in the K-ras and BRAF genes in a cohort of Chinese patients with colorectal cancer (CRC) for their association with various clinicopathological parameters and prognosis.METHODS:Genomic DNA was isolated from frozen tissues.Pyrosequencing analysis was conducted to detect mutations in the K-ras (codons 12,13,and 61) and BRAF genes (codon 600).Statistical analysis was carried out using SPSS-15.0 software.RESULTS:Among the 118 colorectal cancer patients,we detected 41 (34.7%) mutations in the K-ras gene.Mutation frequencies at codon 12 and codon 13 were 23.7% (28/118) and 10.2% (12/118),respectively.Only one patient harbored a point mutation at codon 61 (0.8%,1/118).Gender was the only factor that showed an obvious relationship with K-ras gene mutation (female 44.7% vs male 28.2%,P=0.037).Other clinicopathological features,such as age,location of the tumor,tumor differentiation,Tumor,Node and Metastases classification,and the Union for International Cancer Control staging,showed no positive relationship with K-ras gene mutations.No significant correlation was observed between the presence of K-ras mutations (codons 12,13,and 61) and the survival of the patients.BRAF mutations were rare,and only two patients (1.7%) harbored a detectable mutation at codon 600.CONCLUSION:K-ras gene mutation is a common event in our 118 Chinese CRC patients,with an obvious relationship with gender.However,it seems not to be an independent prognostic factor in CRC patients.The BRAF gene is rarely mutated in Chinese CRC patients.展开更多
Objective:Signet ring cell carcinoma is a rare subtype of colorectal carcinoma(CRC)with an associated BRAFV600E mutation.We investigated frequencies of BRAF mutation in 28 CRCs containing variable signet ring cell com...Objective:Signet ring cell carcinoma is a rare subtype of colorectal carcinoma(CRC)with an associated BRAFV600E mutation.We investigated frequencies of BRAF mutation in 28 CRCs containing variable signet ring cell component and their relation with clinicopathologic parameters.Methods:According to the presence of signet ring cell component,tumors were categorized into groups as follows:0%–9%,10%–24%,25%–49%,and>50%.Genomic DNA was isolated and analyzed for BRAF V600E gene mutation by polymerase chain reaction-restriction fragment length polymorphism.Eleven of 28 cases(39.3%)showed BRAFV600E mutation,which was also confirmed by Sanger sequencing.To elucidate the importance of existence of signet ring cell component at the molecular level,we separated cases into two groups with cut-off levels of 10%and 50%,which pertain to percentages of signet ring cells.Results:Seven of 19 cases(36.8%)under the threshold of 50%and four of nine cases(44.4%)over this threshold value demonstrated BRAF mutation.Three of 7 cases(42.8%)featuring<10%signet ring cell component and eight out of 21 cases(38.1%)showing>10%were BRAF mutated.Conclusions:BRAF mutation must be closely associated with the presence of malignant signet ring cells regardless of their percentages.展开更多
AIM: To investigate the impact of RAS and BRAF mutations on the pattern of metastatic disease and carcinoembryonic antigen(CEA) production.METHODS: In this retrospective study, we investigated the impact of RAS and BR...AIM: To investigate the impact of RAS and BRAF mutations on the pattern of metastatic disease and carcinoembryonic antigen(CEA) production.METHODS: In this retrospective study, we investigated the impact of RAS and BRAF mutational status on pattern of metastatic disease and CEA production. Only patients presenting with a newly diagnosed metastatic colorectal cancer(CRC) were included. Patients' characteristics, primary tumor location, site of metastatic disease and CEA at presentation were compared between those with and without RAS and BRAF mutations.RESULTS: Among 174 patients, mutations in KRAS, NRAS and BRAF were detected in 47%, 3% and 6% respectively. RAS mutations(KRAS and NRAS) were more likely to be found in African American patients(87% vs 13%; P value = 0.0158). RAS mutations were associated with a higher likelihood of a normal CEA(< 5 ng/mL) at presentation. BRAF mutations were more likely to occur in females. We were not able to confirm any association between mutational status and site of metastatic disease at initial diagnosis.CONCLUSION: No association was found between RAS and BRAF mutations and sites of metastatic disease at the time of initial diagnosis in our cohort. Patients with RAS mutations were more likely to present with CEA levels < 5 ng/mL. These findings may have clinical implications on surveillance strategies for RAS mutant patients with earlier stages of CRC.展开更多
AIM:To evaluate the clinicopathological features ofcolorectal cancer(CRC)with a v-Raf murine sarcomaviral oncogene homolog B1(BRAF)mutation and itsmolecular interaction with microsatellite instability(MSI)and v-Ki-ras...AIM:To evaluate the clinicopathological features ofcolorectal cancer(CRC)with a v-Raf murine sarcomaviral oncogene homolog B1(BRAF)mutation and itsmolecular interaction with microsatellite instability(MSI)and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog(KRAS)in patients with advanced CRCs.METHODS:From October 2009 to December 2011,141 patients with stageⅢ(n=51)orⅣ(n=90)CRCs who were tested for the BRAF mutation at Severance Hospital were included.Among 141 patients,fivewere excluded due to follow-up loss.Therefore,136patients were included in the study.The clinicopathological data,MSI status,and KRAS/BRAF mutation status were reviewed retrospectively.In addition,to evaluating the value of BRAF mutation status,progressionfree survival and overall survival in all patients werecollected and compared between the BRAF wild-typegroup and BRAF mutation group.RESULTS:Of 136 patients,80(58.8%)were male and the mean age was 59 years.BRAF and KRAS mutations were detected in 9.6%and 35.3%of patients,respectively.Only 4.3%of patients had MSIhigh tumors and there were no MSI-high in tumors with a BRAF mutation.BRAF mutations tended to be more frequent in stageⅣthan in stageⅢ(11.76%vs 5.88%,P=0.370).Patients with a BRAF mutation had a lower incidence of KRAS mutation than those without(7.69%vs 38.21%,P=0.033).Overall survival was significantly shorter in the BRAF mutation group than in the BRAF wild-type group both by univariate analysis(P=0.041)and multivariate analysis(HR=2.195;95%CI:1.039-4.640;P=0.039),while progression-free survival was not different according to BRAF mutation status.CONCLUSION:CRCs with a BRAF mutation have distinct molecular features and resulted in a poor prognosis in Korean patients with advanced CRC.展开更多
Cancer of the corpus uteri remains the most common gynecological related cancer in developed countries. Cytology, after the induction of liquid based cytology, has reemerged as a possible first line non-interventional...Cancer of the corpus uteri remains the most common gynecological related cancer in developed countries. Cytology, after the induction of liquid based cytology, has reemerged as a possible first line non-interventional diagnostic procedure with promising results. Apart from slide preparation for cytology diagnosis, LBC allows the application of elaborate molecular tests on the residual material. Samples from 74 symptomatic women were collected in ThinPrep?PreservCyt medium, from witch immunocytochemical and molecular tests were performed. Final diagnosis of 39 endometrioid carcinomas, 20 non-endometrioid carcinomas and 15 non-malignant was set after hysterectomy. Topoisomerase IIa expression was common (42%) in both types of cancer. Promoter methylation analysis revealed that hMLH1 is commonly methylated in cancers (52.7%), CDKN2A and MGMT less often (27.1%) and RARB rarely methylated (8.4%). BRAF activating mutation V600E was a rare event (8.4%) only found in low grade endometrioid carcinomas. Topoisomerase IIa expression correlated with BRAF mutations, hMLH1 and to lesser extent with CDKN2A methylation. Almost none of the biomarkers were positive in cytological negative or hyperplastic without atypia samples. Detection of methylation in any gene displayed sensitivity, specificity, PPV and NPV similar to cytology of cancer. However, inclusion of cytology diagnosis of hyperlasias with atypia increased sensitivity and NPV of cytology outperforming methylation of any gene. Further evaluation of the panel of promoter methylation, especially in cytology diagnoses of hyperplasia with or without atypia should be evaluated since initial results are promising. Even though methylation of MGMT and RARB are rare events, some patients could be benefit from specific chemotherapeutics that target either of them or the more frequently expressed topoisomerase IIa.展开更多
Objective The aim of this study was to explore the clinical significance of the expression of proteins human bone marrow endothelial cell markers(HBME-1), Galectin-3, and cytokeratin19(CK19), as well as the status of ...Objective The aim of this study was to explore the clinical significance of the expression of proteins human bone marrow endothelial cell markers(HBME-1), Galectin-3, and cytokeratin19(CK19), as well as the status of v-raf murine sarcoma viral oncogene homolog B1(BRAF) mutation in papillary thyroid carcinoma(PTC). Methods Immunohistochemical staining was performed in 82 specimens each of PTC and papillary benign lesions to detect the expression of HBME-1, Galectin-3, and CK19. Polymerase chain reaction(PCR) and gene sequencing were performed on 60 specimens each of PTC and papillary benign lesions to detect the status of BRAF mutation. Results The positive expression ratios of HBME-1, Galectin-3, and CK19 in PTC were 98.8%, 97.6% and 100% respectively, which were significantly higher than the expressions in papillary benign lesions(P < 0.05). No significant relationship was observed between the expression of these makers and the clinicopathological features of PTC. The sensitivity of co-expression of HBME-1 and CK19 or HBME-1 and Galectin-3 as diagnostic criteria of PTC was 99.9%, with a specificity of 95.4%. BRAF mutation was detected in 40 of 60 PTC(66.7%) specimens. There was a statistical difference in BRAF mutations between PTC and papillary benign lesions(P < 0.05); there were no associations between BRAF mutation and the clinicopathological features of PTC. Conclusion Combined immunohistochemical staining of HBME-1, Galectin-3, and CK19 can further improve the sensitivity and specificity of differential diagnosis of PTC. BRAF mutation is a significant genetic event, which may have diagnostic value for PTC.展开更多
Background:KRAS/BRAF mutations(mutKRAS/mutBRAF)are unfavorable prognostic factors for colorectal cancer(CRC)metastases to the liver and lungs.However,their effects on the prognosis for patients with synchronous perito...Background:KRAS/BRAF mutations(mutKRAS/mutBRAF)are unfavorable prognostic factors for colorectal cancer(CRC)metastases to the liver and lungs.However,their effects on the prognosis for patients with synchronous peritoneal metastasis(S-PM)of CRC after cytoreductive surgery(CRS)and hyperthermic intraperitoneal chemotherapy(HIPEC)are controversial.In the study,we aimed to determine the effects of mutKRAS/mutBRAF on the prognosis for patients with S-PM who received CRS.Methods:A total of 142 patients diagnosed with S-PM between July 2007 and July 2019 were included in this study.The demographics,mutKRAS/mutBRAF status,overall survival(OS),and progression-free survival(PFS)of the patients were evaluated.The Kaplan–Meier method and log-rank test were used to estimate the difference in survival between groups.Results:Among 142 patients,68(47.9%)showed mutKRAS and 42(29.5%)showed mutBRAF.The median OS values were 8.4 and 34.3 months for patients with mutBRAF and BRAF wild-type,respectively(P<0.01).However,KRAS status was not significantly associated with median OS(P=0.76).Multivariate analysis revealed carcinoembryonic antigen,CRS,HIPEC,and mutBRAF as independent predictors for OS.Based on these findings,a nomogram was constructed.The C-index was 0.789(95%confidence interval,0.742–0.836),indicating good predictive ability of the model.Furthermore,the 1-and 2-year survival calibration plots showed good agreement between the predicted and actual OS rates.The area under curves of the 1-and 2-year survival predictions based on the nomogram were 0.807 and 0.682,respectively.Additionally,mutBRAF was significantly associated with lower PFS(P<0.001).Conclusions:mutBRAF is an independent prognostic risk factor for S-PM.The established nomogram predicted the OS of patients with CRC having S-PM with high accuracy,indicating its usefulness as a valuable prognostic tool for the designated patient cohort.展开更多
文摘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.
基金the National Natural Science Foundation of China(No.81472707)Chinese South Western Oncology Group(CSWOG-CCET005).
文摘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.
基金Supported by Japanese Ministry of Health,Labor and Welfare
文摘AIM: To investigate the prognostic role of KRAS and BRAF mutations after adjustment for microsatellite instability(MSI) status in Japanese colorectal cancer(CRC) population.METHODS: We assessed KRAS and BRAF mutations and MSI status in 813 Japanese patients with curatively resected, stage Ⅰ-Ⅲ CRC and examined associations of these mutations with disease-free survival(DFS) and overall survival(OS) using uni- and multivariate Cox proportional hazards models.RESULTS: KRAS and BRAF mutations were detected in 312(38%) of 812 and 40(5%) of 811 tumors, respectively. KRAS mutations occurred more frequently in females than in males(P = 0.02), while the presence of BRAF mutations was significantly associated with the female gender(P = 0.006), proximal tumor location(P < 0.001), mucinous or poorly differentiated histology(P < 0.001), and MSI-high tumors(P < 0.001). After adjusting for relevant variables, including MSI status, KRAS mutations were associated with poorer DFS(HR = 1.35; 95%CI: 1.03-1.75) and OS(HR = 1.46; 95%CI: 1.09-1.97). BRAF mutations were poor prognostic factors for DFS(HR = 2.20; 95%CI: 1.19-4.06) and OS(HR = 2.30; 95%CI: 1.15-4.71). Neither the BRAF by MSI interaction test nor the KRAS by MSI interaction test yielded statistically significant results for DFS and OS.CONCLUSION: KRAS and BRAF mutations are associated with inferior survival, independent of MSI status, inJapanese patients with curatively resected CRC.
基金Supported by The Department of Education of Zhejiang Province of China,grant No.Y200804314the Zhejiang Provincial Natural Science Foundation,grant No.R2090353+1 种基金the Department of Science and Technology of Zhejiang Province,grant No.2008C33039the Chinese Ministry of Health,grant No.N20100148
文摘AIM:To identify and assess mutations in the K-ras and BRAF genes in a cohort of Chinese patients with colorectal cancer (CRC) for their association with various clinicopathological parameters and prognosis.METHODS:Genomic DNA was isolated from frozen tissues.Pyrosequencing analysis was conducted to detect mutations in the K-ras (codons 12,13,and 61) and BRAF genes (codon 600).Statistical analysis was carried out using SPSS-15.0 software.RESULTS:Among the 118 colorectal cancer patients,we detected 41 (34.7%) mutations in the K-ras gene.Mutation frequencies at codon 12 and codon 13 were 23.7% (28/118) and 10.2% (12/118),respectively.Only one patient harbored a point mutation at codon 61 (0.8%,1/118).Gender was the only factor that showed an obvious relationship with K-ras gene mutation (female 44.7% vs male 28.2%,P=0.037).Other clinicopathological features,such as age,location of the tumor,tumor differentiation,Tumor,Node and Metastases classification,and the Union for International Cancer Control staging,showed no positive relationship with K-ras gene mutations.No significant correlation was observed between the presence of K-ras mutations (codons 12,13,and 61) and the survival of the patients.BRAF mutations were rare,and only two patients (1.7%) harbored a detectable mutation at codon 600.CONCLUSION:K-ras gene mutation is a common event in our 118 Chinese CRC patients,with an obvious relationship with gender.However,it seems not to be an independent prognostic factor in CRC patients.The BRAF gene is rarely mutated in Chinese CRC patients.
文摘Objective:Signet ring cell carcinoma is a rare subtype of colorectal carcinoma(CRC)with an associated BRAFV600E mutation.We investigated frequencies of BRAF mutation in 28 CRCs containing variable signet ring cell component and their relation with clinicopathologic parameters.Methods:According to the presence of signet ring cell component,tumors were categorized into groups as follows:0%–9%,10%–24%,25%–49%,and>50%.Genomic DNA was isolated and analyzed for BRAF V600E gene mutation by polymerase chain reaction-restriction fragment length polymorphism.Eleven of 28 cases(39.3%)showed BRAFV600E mutation,which was also confirmed by Sanger sequencing.To elucidate the importance of existence of signet ring cell component at the molecular level,we separated cases into two groups with cut-off levels of 10%and 50%,which pertain to percentages of signet ring cells.Results:Seven of 19 cases(36.8%)under the threshold of 50%and four of nine cases(44.4%)over this threshold value demonstrated BRAF mutation.Three of 7 cases(42.8%)featuring<10%signet ring cell component and eight out of 21 cases(38.1%)showing>10%were BRAF mutated.Conclusions:BRAF mutation must be closely associated with the presence of malignant signet ring cells regardless of their percentages.
文摘AIM: To investigate the impact of RAS and BRAF mutations on the pattern of metastatic disease and carcinoembryonic antigen(CEA) production.METHODS: In this retrospective study, we investigated the impact of RAS and BRAF mutational status on pattern of metastatic disease and CEA production. Only patients presenting with a newly diagnosed metastatic colorectal cancer(CRC) were included. Patients' characteristics, primary tumor location, site of metastatic disease and CEA at presentation were compared between those with and without RAS and BRAF mutations.RESULTS: Among 174 patients, mutations in KRAS, NRAS and BRAF were detected in 47%, 3% and 6% respectively. RAS mutations(KRAS and NRAS) were more likely to be found in African American patients(87% vs 13%; P value = 0.0158). RAS mutations were associated with a higher likelihood of a normal CEA(< 5 ng/mL) at presentation. BRAF mutations were more likely to occur in females. We were not able to confirm any association between mutational status and site of metastatic disease at initial diagnosis.CONCLUSION: No association was found between RAS and BRAF mutations and sites of metastatic disease at the time of initial diagnosis in our cohort. Patients with RAS mutations were more likely to present with CEA levels < 5 ng/mL. These findings may have clinical implications on surveillance strategies for RAS mutant patients with earlier stages of CRC.
文摘AIM:To evaluate the clinicopathological features ofcolorectal cancer(CRC)with a v-Raf murine sarcomaviral oncogene homolog B1(BRAF)mutation and itsmolecular interaction with microsatellite instability(MSI)and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog(KRAS)in patients with advanced CRCs.METHODS:From October 2009 to December 2011,141 patients with stageⅢ(n=51)orⅣ(n=90)CRCs who were tested for the BRAF mutation at Severance Hospital were included.Among 141 patients,fivewere excluded due to follow-up loss.Therefore,136patients were included in the study.The clinicopathological data,MSI status,and KRAS/BRAF mutation status were reviewed retrospectively.In addition,to evaluating the value of BRAF mutation status,progressionfree survival and overall survival in all patients werecollected and compared between the BRAF wild-typegroup and BRAF mutation group.RESULTS:Of 136 patients,80(58.8%)were male and the mean age was 59 years.BRAF and KRAS mutations were detected in 9.6%and 35.3%of patients,respectively.Only 4.3%of patients had MSIhigh tumors and there were no MSI-high in tumors with a BRAF mutation.BRAF mutations tended to be more frequent in stageⅣthan in stageⅢ(11.76%vs 5.88%,P=0.370).Patients with a BRAF mutation had a lower incidence of KRAS mutation than those without(7.69%vs 38.21%,P=0.033).Overall survival was significantly shorter in the BRAF mutation group than in the BRAF wild-type group both by univariate analysis(P=0.041)and multivariate analysis(HR=2.195;95%CI:1.039-4.640;P=0.039),while progression-free survival was not different according to BRAF mutation status.CONCLUSION:CRCs with a BRAF mutation have distinct molecular features and resulted in a poor prognosis in Korean patients with advanced CRC.
文摘Cancer of the corpus uteri remains the most common gynecological related cancer in developed countries. Cytology, after the induction of liquid based cytology, has reemerged as a possible first line non-interventional diagnostic procedure with promising results. Apart from slide preparation for cytology diagnosis, LBC allows the application of elaborate molecular tests on the residual material. Samples from 74 symptomatic women were collected in ThinPrep?PreservCyt medium, from witch immunocytochemical and molecular tests were performed. Final diagnosis of 39 endometrioid carcinomas, 20 non-endometrioid carcinomas and 15 non-malignant was set after hysterectomy. Topoisomerase IIa expression was common (42%) in both types of cancer. Promoter methylation analysis revealed that hMLH1 is commonly methylated in cancers (52.7%), CDKN2A and MGMT less often (27.1%) and RARB rarely methylated (8.4%). BRAF activating mutation V600E was a rare event (8.4%) only found in low grade endometrioid carcinomas. Topoisomerase IIa expression correlated with BRAF mutations, hMLH1 and to lesser extent with CDKN2A methylation. Almost none of the biomarkers were positive in cytological negative or hyperplastic without atypia samples. Detection of methylation in any gene displayed sensitivity, specificity, PPV and NPV similar to cytology of cancer. However, inclusion of cytology diagnosis of hyperlasias with atypia increased sensitivity and NPV of cytology outperforming methylation of any gene. Further evaluation of the panel of promoter methylation, especially in cytology diagnoses of hyperplasia with or without atypia should be evaluated since initial results are promising. Even though methylation of MGMT and RARB are rare events, some patients could be benefit from specific chemotherapeutics that target either of them or the more frequently expressed topoisomerase IIa.
文摘Objective The aim of this study was to explore the clinical significance of the expression of proteins human bone marrow endothelial cell markers(HBME-1), Galectin-3, and cytokeratin19(CK19), as well as the status of v-raf murine sarcoma viral oncogene homolog B1(BRAF) mutation in papillary thyroid carcinoma(PTC). Methods Immunohistochemical staining was performed in 82 specimens each of PTC and papillary benign lesions to detect the expression of HBME-1, Galectin-3, and CK19. Polymerase chain reaction(PCR) and gene sequencing were performed on 60 specimens each of PTC and papillary benign lesions to detect the status of BRAF mutation. Results The positive expression ratios of HBME-1, Galectin-3, and CK19 in PTC were 98.8%, 97.6% and 100% respectively, which were significantly higher than the expressions in papillary benign lesions(P < 0.05). No significant relationship was observed between the expression of these makers and the clinicopathological features of PTC. The sensitivity of co-expression of HBME-1 and CK19 or HBME-1 and Galectin-3 as diagnostic criteria of PTC was 99.9%, with a specificity of 95.4%. BRAF mutation was detected in 40 of 60 PTC(66.7%) specimens. There was a statistical difference in BRAF mutations between PTC and papillary benign lesions(P < 0.05); there were no associations between BRAF mutation and the clinicopathological features of PTC. Conclusion Combined immunohistochemical staining of HBME-1, Galectin-3, and CK19 can further improve the sensitivity and specificity of differential diagnosis of PTC. BRAF mutation is a significant genetic event, which may have diagnostic value for PTC.
基金The Sixth Affiliated Hospital,Sun Yat-Sen University Clinical Research 1010 Program[1010CG(2022)-08]Sun Yat-sen University Clinical Reacher 5010 Program[2017008]supported by National Key Clinical Discipline and the program of Guangdong Provincial Clinical Research Center for Digestive Diseases[2020B1111170004].
文摘Background:KRAS/BRAF mutations(mutKRAS/mutBRAF)are unfavorable prognostic factors for colorectal cancer(CRC)metastases to the liver and lungs.However,their effects on the prognosis for patients with synchronous peritoneal metastasis(S-PM)of CRC after cytoreductive surgery(CRS)and hyperthermic intraperitoneal chemotherapy(HIPEC)are controversial.In the study,we aimed to determine the effects of mutKRAS/mutBRAF on the prognosis for patients with S-PM who received CRS.Methods:A total of 142 patients diagnosed with S-PM between July 2007 and July 2019 were included in this study.The demographics,mutKRAS/mutBRAF status,overall survival(OS),and progression-free survival(PFS)of the patients were evaluated.The Kaplan–Meier method and log-rank test were used to estimate the difference in survival between groups.Results:Among 142 patients,68(47.9%)showed mutKRAS and 42(29.5%)showed mutBRAF.The median OS values were 8.4 and 34.3 months for patients with mutBRAF and BRAF wild-type,respectively(P<0.01).However,KRAS status was not significantly associated with median OS(P=0.76).Multivariate analysis revealed carcinoembryonic antigen,CRS,HIPEC,and mutBRAF as independent predictors for OS.Based on these findings,a nomogram was constructed.The C-index was 0.789(95%confidence interval,0.742–0.836),indicating good predictive ability of the model.Furthermore,the 1-and 2-year survival calibration plots showed good agreement between the predicted and actual OS rates.The area under curves of the 1-and 2-year survival predictions based on the nomogram were 0.807 and 0.682,respectively.Additionally,mutBRAF was significantly associated with lower PFS(P<0.001).Conclusions:mutBRAF is an independent prognostic risk factor for S-PM.The established nomogram predicted the OS of patients with CRC having S-PM with high accuracy,indicating its usefulness as a valuable prognostic tool for the designated patient cohort.
