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Genomic characterization reveals distinctmutation landscapes and therapeutic implications in neuroendocrine carcinomas of the gastrointestinal tract

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Cancer Communications 2022年第12期42卷 1367-1386页

作者： Huanwen Wu Zicheng Yu Yueping Liu Lei guo Lianghong Teng lingchuan guo Li Liang Jing Wang Jie Gao Ruiyu Li Ling Yang Xiu Nie Dan Su Zhiyong Liang Department of Pathology State Key Laboratory of Complex Severe and Rare DiseasesMolecular Pathology Research CenterPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730P.R.China Geneplus-Beijing Beijing 102200P.R.China Department of Pathology The Fourth Hospital of Hebei Medical UniversityShijiazhuangHebei 050011P.R.China Department of Pathology Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021P.R.China Department of Pathology Xuanwu HospitalCapital Medical UniversityBeijing 100053P.R.China Department of Pathology The First Affiliated Hospital of Soochow UniversitySuzhouJiangsu 215000P.R.China Department of Pathology Southern Medical UniversityGuangzhouGuangdong 510515P.R.China Department of Pathology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022P.R.China Department of Pathology The Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital)Institute of Basic Medicine and Cancer(IBMC)Chinese Academy of SciencesHangzhouZhejiang 310022P.R.China

Background:Neuroendocrine carcinomas of the gastrointestinal tract(GINECs)remain a disease of grim prognosis with limited therapeutic *** molecular characteristics are still *** study aimed to explore the underlying genetic basis and heterogeneity of ***:Comprehensive genomic analysis using whole-exome sequencing was performed on 143 formalin-fixed,paraffin-embedded samples of surgically resected GI-NEC with a thorough histological *** signatures,somatic mutations,and copy number aberrations were analyzed and compared across anatomic locations and histological *** analysis was conducted to identify the independent ***:In total,143GI-NECswere examined:the stomach,87 cases(60.8%);the esophagus,29 cases(20.3%);the colorectum,20 cases(14.0%);and the small intestine,7 cases(4.9%).Eighty-three(58.0%)and 60(42.0%)cases were subclassified into small cell and large cell subtypes,***-NECs showed distinct genetic alterations from their lung counterparts and non-neuroendocrine carcinomas in the same *** heterogeneity of mutational signatures,somatic mutations,and copy number variations was revealed across anatomic locations rather than histological *** for tumor protein p53(TP53)and retinoblastoma 1(RB1),the most frequently mutated genes in the stomach,esophagus,colorectum,and small intestine were low-density lipoprotein receptor-related protein 1B(LRP1B),notch receptor 1(NOTCH1),adenomatosis polyposis coli(APC),catenin beta 1(CTNNB1),*** in the WNT-β-catenin,NOTCH and erythroblastic leukemia viral oncogene B(ERBB)pathwayswere prevalently identified in gastric,esophageal,and colorectalNECs,***,104(72.7%)GI-NECs harbored putative clinically relevant alterations,and non-gastric location and RB1 bi-allelic inactivation with copy number alterations were identified as two independent poor prognostic ***,we found th

关键词： Neuroendocrine carcinomas Gastrointestinal tract Genomic characterization Heterogeneity Therapeutic implications

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胆总管腺癌伴卵黄囊瘤和绒毛膜癌分化1例

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中华病理学杂志 2024年第1期53卷 95-97页

作者：杜明占童星郭霞郭凌川苏州大学附属第一医院病理科苏州215006

本文报道1例胆总管腺癌伴卵黄囊瘤和绒毛膜癌分化的病例。患者女,52岁。胆总管肿瘤根治标本,肿瘤大部分区域呈管状、乳头状、筛状、微囊性结构,偶见Schiller-Duval小体,细胞呈柱状、立方状,细胞质透明,内含有嗜酸性小体,部分区域呈滋养... 详细信息

本文报道1例胆总管腺癌伴卵黄囊瘤和绒毛膜癌分化的病例。患者女,52岁。胆总管肿瘤根治标本,肿瘤大部分区域呈管状、乳头状、筛状、微囊性结构,偶见Schiller-Duval小体,细胞呈柱状、立方状,细胞质透明,内含有嗜酸性小体,部分区域呈滋养层细胞形态,诊断胆总管腺癌伴卵黄囊瘤和绒毛膜癌分化。免疫组织化学肿瘤成分均表达细胞角蛋白(CK)7、CK18、CK19,部分表达CK20、CD10、CDX2;p53弥漫强阳性,MSH2、MSH6、MLH1、PMS2均阳性。卵黄囊瘤成分部分表达SALL4、Glypican3,灶性表达甲胎蛋白。绒毛膜癌成分弥漫表达SALL4、人绒毛膜促性腺激素(HCG)。二代测序显示TP53、SMARCA4、U2AF1基因的突变,CDKN2A基因拷贝数缺失,微卫星稳定。术后短期肿瘤进展并伴有肝、肺转移,血清HCG水平显著增高(>12000 IU/L),肝转移肿瘤穿刺结果为绒毛膜癌,患者术后随访7个月,化疗7个周期,生存。

关键词：绒毛膜癌卵黄囊瘤胆总管 CK20 肿瘤进展穿刺结果甲胎蛋白肺转移

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伴导管分化的食管癌临床病理学特征观察

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中华病理学杂志 2023年第8期52卷 802-807页

作者：杜明占郭凌川何晓顺郭霞苏州大学附属第一医院病理科苏州215006

目的探讨伴导管分化的食管癌的临床病理学特征。方法对苏州大学附属第一医院2012—2022年诊断的8例伴导管分化的食管癌的临床特征、形态学特点、免疫组织化学特点以及随访信息总结分析。结果8例中男女各4例;平均年龄68.5岁(59~82岁);2... 详细信息

目的探讨伴导管分化的食管癌的临床病理学特征。方法对苏州大学附属第一医院2012—2022年诊断的8例伴导管分化的食管癌的临床特征、形态学特点、免疫组织化学特点以及随访信息总结分析。结果8例中男女各4例;平均年龄68.5岁(59~82岁);2例位于食管中段,5例位于下段,1例位于贲门处(SiewertⅡ型)。平均直径2.4 cm(0.6~4.5 cm)。肿瘤镜下呈腺样形态,具有双层上皮结构,包含内层腔面上皮与外层基底上皮。内层腔面上皮免疫组织化学细胞角蛋白(CK)7、CK18均阳性。外层基底上皮p40、p63与CK5/6均阳性,平滑肌肌动蛋白、Calponin、CD117均阴性。双层上皮均可见p53呈突变型(弥漫强阳性6/8;缺失表达2/8)。所有病例表面鳞状上皮均未见柱状上皮化生、肠上皮化生以及胃黏膜异位。平均随访时间21.5个月(5~51个月),其中7例存活,1例术后31个月因肿瘤复发及肝转移去世。结论伴导管分化的食管癌是一种少见的食管肿瘤,具有独特的组织形态和免疫组织化学特点。

关键词：食管肿瘤诊断,鉴别伴导管分化的癌

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Real-world data on ALK rearrangement test in Chinese advanced non-small cell lung cancer(RATICAL):a nationwide multicenter retrospective study

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Cancer Communications 2024年第9期44卷 992-1004页

作者： Lin Li Wencai Li ChunyanWu Yanfeng Xi Lei guo Yuan Ji Lili Jiang Ji Li Jingping Yun Gang Chen Yuan Li Yueping Liu DianbinMu Yuchen Han Leina Sun Qingxin Xia Xiaodong Teng Nanying Che WeiWu Xueshan Qiu Chao Liu Xiaochu Yan Daiqiang Li Zhihong Zhang ZheWang Yujun Li ZhengWang lingchuan guo Xiu Nie Jingshu Geng Jianhua Zhou Jianming Ying Department of Pathology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking UnionMedical CollegeBeijingP.R.China Department of Pathology the First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanP.R.China Department of Pathology Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghaiP.R.China Department of Pathology Cancer Hospital Affiliated to Shanxi Medical UniversityShanxi Province Cancer HospitalShanxi Hospital Affiliated to Cancer HospitalChinese Academy of Medical SciencesTaiyuanShanxiP.R.China Department of Pathology Zhongshan HospitalFudan UniversityShanghaiP.R.China Department of Pathology West China Hospital of Sichuan UniversityChengduSichuanP.R.China Department of Pathology Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP.R.China Department of Pathology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdongP.R.China Department of Pathology Fujian Cancer HospitalFujian Medical University Cancer HospitalFuzhouFujianP.R.China Department of Pathology Department of OncologyFudan University Cancer CenterShanghaiMedical College of Fudan UniversityShanghaiP.R.China Department of Pathology The Fourth Hospital of Hebei Medical UniversityShijiazhuangHebeiP.R.China Department of Pathology Shandong Cancer HospitalJinanShandongP.R.China Department of Pathology Shanghai Chest HospitalShanghai Jiao Tong UniversityShanghaiP.R.China Department of Pathology Tianjin Medical University Cancer Institute and HospitalTianjinP.R.China Department of Pathology the Affiliated Cancer Hospital of Zhengzhou UniversityHenan Provincial Cancer HospitalZhengzhouHenanP.R.China Department of Pathology the First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouZhejiangP.R.China Department of Pathology Bei

Background:Anaplastic lymphoma kinase(ALK)test in advanced non-small cell lung cancer(NSCLC)can help physicians provide target therapies for patients harboring ALK gene *** study aimed to investigate the real-world test patterns and positive rates of ALK gene rearrangements in advanced ***:In this real-world study(ChiCTR2000030266),patientswith advanced NSCLC who underwent an ALK rearrangement test in 30 medical centers in China between October 1,2018 and December 31,2019 were retrospectively *** training was conducted before the study was *** controls were performed at participating centers using immunohistochemistry(IHC)-*** positive ALK gene rearrangement rate and consistency rate were *** associated clinicopathological characteristics of ALK gene rearrangement were investigated as ***:The overall ALK gene rearrangement rate was 6.7%in 23,689 patients with advanced NSCLC and 8.2%in 17,436 patients with advanced lung *** quality control analysis of IHC-VENTANA-D5F3 revealed an intrahospital consistency rate of 98.2%(879/895)and an inter-hospital consistency rate of 99.2%(646/651).IHC-VENTANA-D5F3 was used in 53.6%,real-time polymerase chain reaction(RT-PCR)in 25.4%,next-generation sequencing(NGS)in 18.3%,and fluorescence in-situ hybridization(FISH)in 15.9%in the adenocarcinoma *** specimens tested with multiple methods,the consistency rates confirmed by IHC-VENTANA-D5F3 were 98.0%(822/839)for FISH,98.7%(1,222/1,238)forNGS,and 91.3%(146/160)for *** overall ALK gene rearrangement rateswere higher in females,patients of≤35 years old,never smokers,tumor cellularity of>50,and metastatic specimens used for testing in the total NSCLC population and adenocarcinoma subgroup(all P<0.05).Conclusions:This study highlights the real-world variability and challenges of ALK test in advanced NSCLC,demonstrating a predominant use of IHCVENTANA-D5F3 with high co

关键词： anaplastic lymphoma kinase diagnosis gene fusion non-small cell lung cancer

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血管免疫母细胞性T细胞淋巴瘤临床病理及分子遗传与治疗研究进展

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中华病理学杂志 2023年第2期52卷 189-193页

作者：郑浩东王玉红郭凌川苏州大学附属第一医院病理科苏州215006

血管免疫母细胞性T细胞淋巴瘤(AITL)是一种独特的外周T细胞淋巴瘤亚型,仅占非霍奇金淋巴瘤的1%~2%,其主要病理形态特点为滤泡树突状细胞和高内皮小静脉显著增生,伴多形性炎性细胞浸润,小-中等大小透亮肿瘤细胞簇状增生围绕于血管周围。... 详细信息

血管免疫母细胞性T细胞淋巴瘤(AITL)是一种独特的外周T细胞淋巴瘤亚型,仅占非霍奇金淋巴瘤的1%~2%,其主要病理形态特点为滤泡树突状细胞和高内皮小静脉显著增生,伴多形性炎性细胞浸润,小-中等大小透亮肿瘤细胞簇状增生围绕于血管周围。近年来学者们通过高通量测序或临床前模型等方法,对AITL的发病机制尤其是分子遗传学机制做了深入研究,进一步揭示了各基因突变的潜在作用机制。AITL总体预后差,生存期短,传统化疗方案总体生存率低。但随着对AITL分子遗传机制的不断深入研究,一些新型药物或疗法已尝试用于复发难治性AITL患者,取得了一定的疗效。本文旨在归纳总结AITL的临床病理特征及其分子遗传机制的研究进展,以加强对该病的充分认识,并对其治疗策略的研究进展做汇总综述,为临床诊治AITL提供一些参考。

关键词：非霍奇金淋巴瘤外周T细胞淋巴瘤滤泡树突状细胞病理形态特点炎性细胞浸润总体生存率潜在作用基因突变

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Risk assessment and early warning of imported COVID-19 in 21 cities, Guangdong province

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中华流行病学杂志 2020年第5期 658-662页

作者： Hu Jianxiong Liu Tao Xiao Jianpeng He Guanhao Rong Zuhua Yin Lihua Wan Donghua Zeng Weilin Gong Dexin guo lingchuan Zhu Zhihua Zeng Lilian Kang Min Song Tie Zhong Haojie He Jianfeng Sun Limei Li Yan Ma Wenjun Guangdong Provincial Institute of Public Health Guangdong Provincial Center for Disease Control and Prevention Guangzhou 511430 China China

Objective To assess the imported risk of COVID-19 in Guangdong province and its cities, and conduct early *** Data of reported COVID-19 cases and Baidu Migration Index of 21 cities in Guangdong province and other provinces of China as of February 25, 2020 were collected. The imported risk index of each city in Guangdong province were calculated, and then correlation analysis was performed between reported cases and the imported risk index to identify lag time. Finally, we classified the early warming levels of epidemic by imported risk *** A total of 1 347 confirmed cases were reported in Guangdong province, and 90.0% of the cases were clustered in the Pearl River Delta region. The average daily imported risk index of Guangdong was 44.03. Among the imported risk sources of each city, the highest risk of almost all cities came from Hubei province, except for Zhanjiang from Hainan province. In addition, the neighboring provinces of Guangdong province also had a greater impact. The correlation between the imported risk index with a lag of 4 days and the daily reported cases was the strongest (correlation coefficient: 0.73). The early warning base on cumulative 4-day risk of each city showed that Dongguan, Shenzhen, Zhongshan, Guangzhou, Foshan and Huizhou have high imported risks in the next 4 days, with imported risk indexes of 38.85, 21.59, 11.67, 11.25, 6.19 and 5.92, and the highest risk still comes from Hubei *** Cities with a large number of migrants in Guangdong province have a higher risk of import. Hubei province and neighboring provinces in Guangdong province are the main source of the imported risk. Each city must strengthen the health management of migrants in high-risk provinces and reduce the imported risk of Guangdong province.

关键词： COVID-19 Risk assessment Early warning

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伴肠母细胞分化的胃腺癌并肝转移1例

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中华病理学杂志 2022年第8期51卷 768-770页

作者：杜明占郭凌川王玉红苏州大学附属第一医院病理科苏州215006

伴肠母细胞分化的胃腺癌合并绒毛膜癌成分并肝转移病例比较罕见。患者为65岁女性。胃癌根治标本, 胃肿瘤呈腺管状、乳头状结构, 细胞质透明, 诊断为伴肠母细胞分化的胃腺癌。在淋巴结转移灶和肝转移灶中出现了绒毛膜癌成分。免疫组织化... 详细信息

伴肠母细胞分化的胃腺癌合并绒毛膜癌成分并肝转移病例比较罕见。患者为65岁女性。胃癌根治标本, 胃肿瘤呈腺管状、乳头状结构, 细胞质透明, 诊断为伴肠母细胞分化的胃腺癌。在淋巴结转移灶和肝转移灶中出现了绒毛膜癌成分。免疫组织化学不同程度表达SALL4、Glypican3、甲胎蛋白、人绒毛膜促性腺激素、CDX2、CD10等抗体。二代测序提示TP53突变、MYC扩增等改变。此肿瘤恶性程度高, 预后差, 对术前化疗不敏感。患者术后12个月死亡。

关键词：绒毛膜癌胃腺癌肿瘤恶性程度淋巴结转移灶肝转移乳头状结构术前化疗人绒毛膜促性腺激素

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Ambient Temperature and Years of Life Lost:A National Study in China

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The Innovation 2021年第1期2卷 3-10页

作者： Tao Liu Chunliang Zhou Haoming Zhang Biao Huang Yanjun Xu Lifeng Lin Lijun Wang Ruying Hu Zhulin Hou Yize Xiao Junhua Li Xiaojun Xu Donghui Jin Mingfang Qin Qinglong Zhao Weiwei Gong Peng Yin Yiqing Xu Jianxiong Hu Jianpeng Xiao Weilin Zeng Xing Li Siqi Chen lingchuan guo Zuhua Rong Yonghui Zhang Cunrui Huang Yaodong Du Yuming guo Shannon Rutherford Min Yu Maigeng Zhou Wenjun Ma Guangdong Provincial Institute of Public Health Guangdong Provincial Center for Disease Control and PreventionGuangzhou511430China Hunan Provincial Center for Disease Control and Prevention Changsha410005China Yunnan Center for Disease Control and Prevention Kunming650022China Health Hazard Factors Control Department Jilin Provincial Center for Disease Control and PreventionChangchun130062China Guangdong Provincial Center for Disease Control and Prevention Guangzhou511430China The National Center for Chronic and Noncommunicable Disease Control and Prevention Beijing100050China Zhejiang Center for Disease Control and Prevention Hangzhou310051China School of Public Health Sun Yat-sen UniversityGuangzhou510080China Guangdong Provincial Climate Center Guangzhou510080China Department of Epidemiology and Preventive Medicine School of Public Health and Preventive MedicineMonash UniversityMelbourne3800Australia School of Medicine Griffith UniversityGold Coast4214Australia

Although numerous studies have investigated premature deaths attributable to temperature,effects of temperature on years of life lost(YLL)remain *** estimated the relationship between temperatures and YLL,and quantified the YLL per death caused by temperature in *** collected daily meteorological and mortality data,and calculated the daily YLL values for 364 locations(2013–2017 in Yunnan,Guangdong,Hunan,Zhejiang,and Jilin provinces,and 2006–2011 in other locations)in China.A time-series design with a distributed lag nonlinear model was first employed to estimate the location-specific associations between temperature and YLL rates(YLL/100,000 population),and a multivariate meta-analysis model was used to pool location-specific ***,YLL per death caused by temperatures was *** temperature and YLL rates consistently showed U-shaped associations.A mean of 1.02(95%confidence interval:0.67,1.37)YLL per death was attributable to *** temperature caused 0.98 YLL per death with most from moderate cold(0.84).The mean YLL per death was higher in those with cardiovascular diseases(1.14),males(1.15),younger age categories(1.31 in people aged 65–74 years),and in central China(1.34)than in those with respiratory diseases(0.47),females(0.87),older people(0.85 in people R75 years old),and northern China(0.64)or southern China(1.19).The mortality burden was modified by annual temperature and temperature variability,relative humidity,latitude,longitude,altitude,education attainment,and central heating *** caused substantial YLL per death in China,which was modified by demographic and regional characteristics.

关键词： TEMPERATURE YEARS OF LIFE LOST MORTALITY BURDEN DISTRIBUTED LAG NONLINEAR MODEL MULTIVARIATE META-ANALYSIS CHINA

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EB病毒阳性淋巴上皮瘤样胆管细胞癌3例临床病理学分析

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中华病理学杂志 2023年第8期52卷 841-843页

作者：杜明占郭凌川黄山郭霞朱碧云苏州大学附属第一医院病理科苏州215006 苏州大学附属第一医院放射科苏州215006

目的探讨EB病毒阳性淋巴上皮瘤样胆管细胞癌的临床病理特征。方法收集苏州大学附属第一医院2008—2022年诊断的EB病毒阳性淋巴上皮瘤样胆管细胞癌3例,分析临床特征、HE和免疫组织化学特点并总结。结果3例均为女性;平均年龄53.7岁(51~59... 详细信息

目的探讨EB病毒阳性淋巴上皮瘤样胆管细胞癌的临床病理特征。方法收集苏州大学附属第一医院2008—2022年诊断的EB病毒阳性淋巴上皮瘤样胆管细胞癌3例,分析临床特征、HE和免疫组织化学特点并总结。结果3例均为女性;平均年龄53.7岁(51~59岁);1例位于肝左叶,2例于肝右叶。1例血清乙肝病毒阳性,2例阴性。2例术前血清甲胎蛋白水平正常,1例未测。镜下瘤细胞部分为实性、未分化形态,部分呈腺管状,间质淋巴细胞、浆细胞丰富,部分淋巴滤泡形成。2例伴有普通型胆管细胞癌,显示不规则腺体伴有促纤维性间质及散在淋巴细胞、浆细胞。周围肝组织均未见肝硬化,1例伴有重度脂肪变性。EB病毒阳性淋巴上皮瘤样胆管细胞癌和普通型胆管细胞癌区域,免疫组织化学均细胞角蛋白(CK)7、CK19阳性,错配修复蛋白均提示微卫星稳定,原位杂交检测均提示EB病毒编码的RNA阳性。随访时间4~20个月,均生存。结论EB病毒阳性淋巴上皮瘤样胆管细胞癌是一种少见的肝内肿瘤类型,需EB病毒检测,其具有独特的组织学形态和免疫组织化学特点。

关键词：胆管细胞癌血清甲胎蛋白组织学形态肝左叶肝右叶脂肪变性瘤细胞 EB病毒

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原发性脾脏淋巴瘤手术治疗34例分析

引用

中国肿瘤临床 2012年第3期29卷 153-155页

作者：王毅宋世铎刘丰郭凌川沈益民苏州大学附属第一医院普通外科江苏省苏州市215006 苏州大学附属第一医院病理科江苏省苏州市215006 苏州大学附属第一医院血液科江苏省苏州市215006

目的:探讨原发性脾脏淋巴瘤的外科指征和效果。方法:回顾性分析2002年6月至2010年12月原发性脾脏淋巴瘤34例临床资料。结果:左上腹痛、腹胀13例(38.2%)及B症状5例(14.7%)为原发性脾脏淋巴瘤的主要临床症状。中度及中度以上脾肿大30例(88... 详细信息

目的:探讨原发性脾脏淋巴瘤的外科指征和效果。方法:回顾性分析2002年6月至2010年12月原发性脾脏淋巴瘤34例临床资料。结果:左上腹痛、腹胀13例(38.2%)及B症状5例(14.7%)为原发性脾脏淋巴瘤的主要临床症状。中度及中度以上脾肿大30例(88.2%),Ahmann临床分期Ⅰ期12例(35.3%),Ⅱ期3例(8,8%),Ⅲ期19例(55.9%)。外科手术明确诊断者为12例(35.3%),缓解脾肿大或脾功能亢进症状者为11例(32.4%)。手术方式为29例(85.3%)开腹脾切除术,5例(14.7%)腹腔镜或手助式腹腔镜脾脏切除术。病理为非霍奇金淋巴瘤33例(97.1%),其中B淋巴瘤29例、T淋巴瘤4例。另1例为霍奇金病。术后发生9例(26.5%)并发症,手术死亡4例(11.8%)。结论:脾脏切除术能提高Ⅰ、Ⅱ期原发性脾脏淋巴瘤的生存率,同时能减轻脾肿大引起的不适症状,且有益于进一步明确诊断,腹腔镜或手助式腹腔镜脾切除术有利于原发性脾脏淋巴瘤术后全身情况的恢复。

关键词：淋巴瘤脾肿大脾切除术腹腔镜

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