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胃孤立性朗格汉斯细胞组织细胞增生症一例

中华病理学杂志 2020年第6期49卷 631-633页

作者：李亚男邵世宏赵涵信芳杰潘越赵鹏青岛大学附属医院病理科 266003 青岛大学医学部 266003

朗格汉斯细胞组织细胞增生症(Langerhans cell histiocytosis,LCH)是一种罕见的以朗格汉斯细胞增生为特征的单克隆性疾病。该文报道1例发生于胃的LCH。患者男,59岁。镜下观察肿瘤细胞呈片状及巢状排列,细胞呈圆形及椭圆形,仅部分有核沟... 详细信息

朗格汉斯细胞组织细胞增生症(Langerhans cell histiocytosis,LCH)是一种罕见的以朗格汉斯细胞增生为特征的单克隆性疾病。该文报道1例发生于胃的LCH。患者男,59岁。镜下观察肿瘤细胞呈片状及巢状排列,细胞呈圆形及椭圆形,仅部分有核沟,嗜酸性小核仁可见,背景缺乏淋巴细胞、嗜酸性粒细胞,见大量泡沫样组织细胞,核分裂象约2个/HPF。免疫组织化学表达Langerin、S-100蛋白和CD1α,BRAF V600E为阴性,PCR-免疫荧光法BRAF V600E基因发生突变。胃孤立性LCH是一种肿瘤性病变,确诊依赖于病理学诊断,极易漏诊且需要与黑色素瘤、组织细胞肉瘤等恶性肿瘤相鉴别,临床多给予局部切除的治疗方法。

关键词：朗格汉斯细胞局部切除泡沫样克隆性疾病嗜酸性粒细胞 BRAF 黑色素瘤免疫荧光法

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全身多发淋巴结肿大

中华病理学杂志 2021年第9期50卷 1054-1056页

作者：王正岩谢建兰周小鸽首都医科大学附属北京友谊医院病理科 100050

朗格汉斯细胞组织细胞增生症(LCH)是朗格汉斯细胞的克隆性肿瘤性增殖。好发于儿童,老年人罕见。本文探讨1例发生于老年人的多发淋巴结肿大病例,形态学上肿瘤细胞簇状排列伴有噬血现象。免疫表型支持朗格汉斯细胞来源,分子检测存在BRAF V... 详细信息

朗格汉斯细胞组织细胞增生症(LCH)是朗格汉斯细胞的克隆性肿瘤性增殖。好发于儿童,老年人罕见。本文探讨1例发生于老年人的多发淋巴结肿大病例,形态学上肿瘤细胞簇状排列伴有噬血现象。免疫表型支持朗格汉斯细胞来源,分子检测存在BRAF V600E突变。发生于老年人的LCH伴有噬血现象病例少见,病理诊断缺乏经验,容易误诊或漏诊。

关键词：朗格汉斯细胞多发淋巴结肿大肿瘤性免疫表型克隆性 BRAF 病理诊断分子检测

甲状腺乳头状癌中BRAF基因突变与中央区淋巴结转移的关系及临床意义

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北京大学学报（医学版） 2016年第3期48卷 502-506页

作者：张玉洁刘宝国赵治艳盛今东冯冬冬北京大学临床肿瘤学院北京肿瘤医院暨北京市肿瘤防治研究所头颈外科恶性肿瘤发病机制及转化研究教育部重点实验室北京100142

目的：阐明BRAF基因突变在甲状腺乳头状癌中央区淋巴结转移中的作用。方法：采集整理2012年至2014年间于北京大学肿瘤医院头颈外科行手术治疗的275例甲状腺乳头状癌患者,对其肿瘤组织进行BRAF基因检测并通过单因素、多因素Logistic回归... 详细信息

目的：阐明BRAF基因突变在甲状腺乳头状癌中央区淋巴结转移中的作用。方法：采集整理2012年至2014年间于北京大学肿瘤医院头颈外科行手术治疗的275例甲状腺乳头状癌患者,对其肿瘤组织进行BRAF基因检测并通过单因素、多因素Logistic回归模型探索中央区（Ⅵ区）淋巴结转移的危险因素。结果：275例患者中,女性224例（81.5%）,男性51例（18.5%）。有57.8%（159/275）的患者发生中央区淋巴结转移,BRAF的突变率为53.8%（148/275）,其中,超声下有无钙化（ORadjusted=1.47,95%CI：1.10-1.98,P=0.01）、肿瘤的长径（ORadjusted=1.48,95%CI：1.04-2.30,P=0.048）及患者的年龄（ORadjusted=1.48,95%CI：1.04-2.30,P=0.048）与淋巴结转移显著相关。分层分析后,BRAF突变在超声下边界尚清组（ORadjusted=3.19,95%CI：1.18-9.43,P=0.023）和超声下无钙化组（ORadjusted=4.84,95%CI：1.68-13.84,P=0.003）均与淋巴结转移正相关。结论：甲状腺乳头状癌患者具有一定比例的中央区淋巴结转移率,BRAF突变是甲状腺乳头状癌的特征性分子事件,钙化、低年龄组及肿瘤长径较长的患者更易发生中央区淋巴结转移。尽管超声下边界尚清或无钙化,但一旦合并BRAF突变则更易发生淋巴结转移,中央区淋巴结清扫术是有效的治疗方法。

关键词：甲状腺癌,乳头状淋巴转移 BRAF 突变淋巴结切除术

Relationships among KRAS mutation status, expression of RAS pathway signaling molecules, and clinicopathological features and prognosis of patients with colorectal cancer

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World Journal of Gastroenterology 2019年第7期25卷 808-823页

作者： Xiang-Bin Wan Ai-Qin Wang Jian Cao Zhi-Chuang Dong Ning Li Sen Yang Miao-Miao Sun Zhi Li Su-Xia Luo Department of General Surgery the Affiliated Tumor Hospital of Zhengzhou University Department of Pharmacy The Second Affiliated Hospital of Xinxiang Medical University Department of Medical Oncology the Affiliated Tumor Hospital of Zhengzhou University China-US (Henan) Hormel Cancer Institute Department of Pathology the Affiliated Tumor Hospital of Zhengzhou University

BACKGROUND The RAS/RAF/MEK/ERK and PI3 K/AKT/mTOR signaling pathways all belong to mitogen-activated protein kinase(MAPK) signaling pathways, Mutations in any one of the upstream genes(such as the RAS gene or the BRAF gene) may be transmitted to the protein through transcription or translation, resulting in abnormal activation of the signaling pathway. This study investigated the relationship between the KRAS gene mutation and the clinicopathological features and prognosis of colorectal cancer(CRC), and the effect of KRAS mutations on its associated proteins in CRC, with an aim to clarify the cause of tumor progression and drug resistance caused by mutation of the KRAS gene.AIM To investigate the KRAS gene and RAS pathway signaling molecules in CRC and to analyze their relationship with clinicopathological features and prognosis METHODS Colorectal cancer tissue specimens from 196 patients were analyzed for KRAS mutations using quantitative polymerase chain reaction and for KRAS, BRAF,MEK, and ERK protein expression levels using immunohistochemistry of tumor microarrays. To analyze differences of RAS pathway signaling molecule expression levels in different KRAS gene status, the relationships between these parameters and clinicopathological features, 4-year progression-free survival, and overall survival were analyzed by independent sample t test, Kaplan-Meier plots,and the log-rank test. Predictors of overall and disease-free survival were assessed using a Cox proportional hazards model.RESULTS Of the 196 patients, 62(32%) carried mutations in codon 12(53/62) or codon 13(9/62) in exon 2 of the KRAS gene. KRAS, BRAF, ERK, and MEK protein expression was detected in 71.4%, 78.8%, 64.3%, and 50.8% of CRC tissues,respectively. There were no significant differences between KRAS mutation status and KRAS, BRAF, MEK, or ERK protein levels. Positive expression of KRAS and ERK was associated with poor tumor differentiation, and KRAS expression was also associated with age < 56 years. MEK expression was significantly associa

关键词： Colorectal cancer KRAS gene KRAS protein BRAF protein MEK protein ERK protein

鼠类肉瘤滤过性毒菌致癌同源体B1 V600 E基因突变与甲状腺乳头状癌中央区淋巴结转移的关系

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中华肿瘤杂志 2015年第2期37卷 123-127页

作者：石臣磊秦华东丁超孙宇吕一辰石铁锋哈尔滨医科大学附属第二临床医院普外四科 150086

目的：探讨鼠类肉瘤滤过性毒菌致癌同源体B1（BRAF）V600E基因突变与甲状腺乳头状癌（ PTC）中央区淋巴结转移的关系。方法回顾性分析126例PTC患者的临床病理资料，采用荧光定量PCR检测BRAF V600E基因的突变情况。结果126例PTC患者中，B... 详细信息

目的：探讨鼠类肉瘤滤过性毒菌致癌同源体B1（BRAF）V600E基因突变与甲状腺乳头状癌（ PTC）中央区淋巴结转移的关系。方法回顾性分析126例PTC患者的临床病理资料，采用荧光定量PCR检测BRAF V600E基因的突变情况。结果126例PTC患者中，BRAF V600E基因突变发生率为69．0％（87／126）。单因素分析显示，中央区淋巴结转移与BRAF V600E基因突变有关（P＜0．05），而患者性别、年龄、多发病灶、肿瘤大小、腺外侵及、桥本氏甲状腺炎和肿瘤分期与 BRAF V600E基因突变无关（P＞0．05）。多因素分析显示，只有中央区淋巴结转移与BRAF V600E基因突变有关（P＜0．05）。当肿瘤直径≤10 mm时，BRAF V600E基因突变对中央区淋巴结转移无影响（P＞0．05）；当肿瘤直径＞10 mm时，BRAF V600E基因突变阳性患者的中央区淋巴结转移率显著高于BRAF V600E基因突变阴性患者，差异有统计学意义（P＜0．05）。结论 BRAF V600E基因突变是PTC中央区淋巴结转移风险的独立预测因素。对于术前检测BRAF V600E基因突变阳性的患者，肿瘤直径越大越应该重视中央区淋巴结清扫的重要性，且应该常规清扫该区域淋巴脂肪组织。但当BRAF V600E基因突变阴性患者的肿瘤直径≤5 mm时，应该重新审视中央区淋巴结清扫的必要性。

关键词：甲状腺肿瘤 BRAF V600E基因突变淋巴结肿瘤转移

BRAF V600Q-mutated lung adenocarcinoma with duodenal metastasis and extreme leukocytosis

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World Journal of Clinical Oncology 2017年第4期8卷 360-365页

作者： Ayman Qasrawi Addison Tolentino Mouhanna Abu Ghanimeh Omar Abughanimeh Sakher Albadarin Department of Internal Medicine University of Missouri-Kansas City School of Medicine Saint Luke's Cancer Specialists Saint Luke's Hospital of Kansas City Division of Gastroenterology University of Missouri-Kansas City School of Medicine

Driver mutations in patients with non-small cell lung cancer(NSCLC) can lead to distinct behaviors and patterns of metastasis. Mutations in the proto-oncogene B-raf(BRAF) occur in approximately 3% of NSCLC cases. In the literature, reports of patients with lung adenocarcinomas metastasizing to the duodenum are rare, and most of the only 21 cases reported were from before the advent of next-generation sequencing. We present here a case involving a 57-year-old female who had a lytic lesion in her lesser trochanter. Biopsy showed metastatic adenocarcinoma of lung origin. Chest X-ray showed a large left upper lobe mass. Next-generation sequencing analysis confirmed the presence of BRAF V600 Q mutation. The patient presented with persistent anemia and melena. Esophagogastroduodenoscopy confirmed the presence of duodenal metastasis. She also had suspected paraneoplastic leukemoid reaction. To our knowledge, this is only the second well-documented case of gastrointestinal metastasis from BRAF -mutated lung cancer.

关键词： BRAF Lung adenocarcinoma Duodenum Metastasis Gastrointestinal bleeding Endoscopy Leukocytosis

BRAF V600E突变与甲状腺乳头状癌临床病理相关性研究

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临床耳鼻咽喉头颈外科杂志 2018年第19期32卷 1472-1476页

作者：赵荧王鸿雁王春宝牛蔓汪园园李晓锋西安交通大学第一附属医院病理科西安710061 西安市第四医院病理科西安710004

目的:研究BRAF V600E突变与甲状腺乳头状癌(PTC)临床病理特征的相关性,探讨PTC组织BRAF V600E突变检测的应用价值。方法:采用qPCR方法对108例PTC患者及30例对照组织进行BRAF V600E突变检测,回顾PTC突变型组和野生型组患者的临床病理资料... 详细信息

目的:研究BRAF V600E突变与甲状腺乳头状癌(PTC)临床病理特征的相关性,探讨PTC组织BRAF V600E突变检测的应用价值。方法:采用qPCR方法对108例PTC患者及30例对照组织进行BRAF V600E突变检测,回顾PTC突变型组和野生型组患者的临床病理资料,使用SPSS 21.0软件进行统计学分析。结果:对照组未检测到BRAF V600E突变。108例PTC患者BRAF V600E突变率为72.20%。突变型组患者平均年龄大于野生型组,差异有统计学意义(PBRAF V600E突变与PTC组织亚型有关,与中央区淋巴结转移有关,差异有统计学意义(P0.05)。结论:BRAF V600E突变对PTC预后判断的价值尚待研究,相比于预后判断,对PTC的病理诊断价值更加显著。

关键词：甲状腺肿瘤 BRAF V600E基因病理学检查

RET/RAS/BRAF基因驱动甲状腺乳头状癌共表达关键基因的生物信息学分析

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临床与实验病理学杂志 2021年第6期37卷 727-730页

作者：仇以利陈一峰杨金玲张宏图福建医科大学附属泉州第一医院病理科泉州362000 中国医学科学院肿瘤医院病理科北京100020

目的应用生物信息学方法分析RET/RAS/BRAF基因驱动甲状腺乳头状癌(papillary thyroid carcinoma,PTC)的共表达关键基因。方法从GEO下载数据集GSE58545,利用在线分析GEO2R工具筛选差异表达基因,通过韦恩图交集寻找共表达基因,应用GO、KEG... 详细信息

目的应用生物信息学方法分析RET/RAS/BRAF基因驱动甲状腺乳头状癌(papillary thyroid carcinoma,PTC)的共表达关键基因。方法从GEO下载数据集GSE58545,利用在线分析GEO2R工具筛选差异表达基因,通过韦恩图交集寻找共表达基因,应用GO、KEGG、Matascape等数据库分析共表达基因的功能及通路,应用Cytoscape软件和STRING网络明确关键基因,应用Oncomine数据库分析关键基因的表达,应用Ualcan数据库验证TCGA数据库中关键基因在PTC中的表达趋势及临床病理联系,在HPA数据库确认关键基因编码蛋白在PTC中的表达。结果KEGG、Canonical、Reactome通路分析筛选出来的34个RET/RAS/BRAF基因驱动PTC的共表达基因,分别与转录失调、p53蛋白调控免疫球蛋白死亡结构域、MET信号转导事件有关,从中挖掘出10个关键基因:MET、DPP4、ENTPD1、MUC1、SPINT1、BHLHE40、CLDN1、GALNT7、TGFA、TYMS,进一步由Oncomine和Ualcan数据库的临床病理资料证实关键基因mRNA的表达均显著高于正常组织(PBRAF基因驱动PTC中发挥作用的关联基因成员,为PTC的精准危险度分层拓宽有关基因变异及其分子机制探索,它们有望成为放射性碘难治性或手术不能切除PTC患者潜在的分子标志物及靶点。

关键词：甲状腺肿瘤乳头状癌生物信息学 RET RAS BRAF

Clinical meaning of BRAF mutation in Korean patients with advanced colorectal cancer

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World Journal of Gastroenterology 2014年第15期20卷 4370-4376页

作者： Bun Kim Soo Jung Park Jae Hee Cheon Tae Il Kim Won Ho Kim Sung Pil Hong Department of Internal Medicine Institute of GastroenterologyYonsei University College of MedicineSeoul 120-752South Korea

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.

关键词： BRAF Colorectal cancer Molecular features Chemothe