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北方集成电路技术创新中心（北京）有限公司简介 - EDTM 2021

北方集成电路技术创新中心（北京）有限公司简介 - EDTM 2021

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清华大学

北京未来芯片技术高精尖创新中心

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北方集成电路技术创新中心（北京）有限公司简介

北方集成电路技术创新中心（北京）有限公司由集成电路制造及上下游企业联合组建（以下称“创新中心”或“STIC”）。针对集成电路紧跟国际领先水平，创新中心依托北京地区集成电路产业的优势资源，促进集成电路行业上下游骨干企业、高等院校、科研院所等企事业的合作，致力于成为集成电路供应链和先导技术产业创新中心的实体平台。

创新中心建立自身造血机制，面向市场提供集成电路、半导体有关的芯片制造、技术开发、设计服务、技术服务、技术转让和技术咨询等服务，包括先进技术联合研发、成果授权使用、验证服务、设备租赁、企业孵化等各类定制化科技增值服务。创新中心的主要业务模块：

产业链协同创新。与产业链企业紧密合作，联合开展半导体设备、材料、零部件的基础研究、技术研发、测试验证、批量应用，建立合作新模式，提高共性技术开发的能力。

技术开发与合作。与创新设计企业合作，联合开发有市场潜力的新型产品，满足终端客户需求；与高校院所合作，在新器件、新材料、新工艺、新架构、新机理等方面开展制造技术研究，探索集成电路的特色工艺，与业界共同培养高端专业人才。重点建设创新技术产业化开发能力。

创新技术服务。为小微设计公司、高校院所提供专业的技术指导、成果转化等服务，开展IP技术开发与合作，提供多样化的多项目晶圆、新产品流片等定制服务。

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北方集成电路技术创新中心(北京)有限公司 - 知乎

北方集成电路技术创新中心(北京)有限公司 - 知乎切换模式写文章登录/注册北方集成电路技术创新中心(北京)有限公司海投网​已认证账号投递链接：https://xyzp.haitou.cc/article/2327359.html来源：海投网北方集成电路技术创新中心（北京）有限公司招聘简章

公司简介：

北方集成电路技术创新中心（北京）有限公司，是中芯国际集成电路制造有限公司为突破发展制约，聚集产业创新资源，联合国内顶尖集成电路设计、装备、材料及零部件企业共同组建的研发及技术服务平台，是在国家及北京市支持下，为响应国家创新战略而最早成立的集成电路产业创新中心之一。

创新中心立足自主创新，以制造平台为基础，以技术研发为核心，承担“双肩挑”的创新任务，一肩促进“装备、材料及零部件企业的协同发展”，一肩促进“芯片设计企业的做大做强”，致力于建设以产品工艺研发为主要特色的国家级集成电路综合性产业创新中心。创新中心立足国内产业基础，面向全球高等院校，开展以企业为主体的产学研合作，进行国际最前沿的半导体技术研究。

创新中心业务包括与集成电路、半导体有关的芯片制造、技术开发、设计服务、技术服务、技术转让和技术咨询等。

岗位需求：

工艺整合研发工程师

职位描述：

1.本岗位属于12英寸先进工艺技术研发岗位。主要负责集成电路前沿产业技术先导研究及开发，与创新企业及高校研究所合作开展创新成果产业化验证及转化，并在12英寸大规模集成电路生产线上的工艺实现

2.按照项目要求，完成工艺制程（Process）在12英寸厂的建立、开发、优化，最终实现预期结构及电学功能，形成自主性研发成果。主要研究方向：先进逻辑器件及工艺（TFET/GAA/CIS等）、嵌入式新型存储器集成工艺（RRAM/FeRAM等）、先进封装工艺集成（3D/2.5D/Chiplet等）

3.与光罩生产部门、OPC部门合作，沟通新项目所需光罩OPC信息，确保项目layout数据准确制备出光罩

4.与各工艺工程部门密切沟通，建立研发项目所需的工艺流程，设计实验条件，完成流片验证并测试，实现电学功能

5.与产业链上下游合作，推动先进工艺设备、材料、EDA工具的研发

任职资格：

1.微电子、电子、物理、材料、化学等理工科专业

2.英语六级或以上；具有良好的听说读写能力

3.熟练使用PPT, word, excel等office软件

4.有项目研发思维、创新精神；有责任心，团队合作精神

5.具有集成电路工艺生产、研发或器件开发经验者优先

OPC工程师

职位描述：

1.协助尖端产品光学临近效应修正过程从公司研发部门到光罩厂的技术转让研究，包括程式启动设立，程式运转及监控，程式结果分析以及weak point相关的程式纠错。

2.成熟节点光学临近效应修正产品的问题探究和优化处理。

任职资格：

1.光学、微电子等相关专业

2.掌握OPC建模方法

3.了解霍普金斯衍射积分，能够独立进行source优化与mask optimization

工艺整合工程师

职责描述：

1.主导新工艺技术开发流程，包括技术参数制定，工艺流程建立与优化，设计规则制定与验证。

2.对接客户，进行客户风险评估、需求转化，撰写项目立项及研发进度报告。

3.负责已开发平台技术转移，制定技术转移相关工程文件，主导技术转移流程。

4.研发过程中，负责制定工程实验计划、实验晶圆异常情况处理、电性测试程式编写及结果分析，测试结构设计及验证等。

任职资格：

1.微电子类、化工类、物理类、材料类、 数学类等理工科专业。

2.具备良好的沟通能力和团队协作能力。

3.熟悉PN结，BJT，MOSFET等基本半导体器件特性，了解半导体制造基本流程。

4.熟悉刻蚀工艺及设备，熟悉Foundry流片流程，能够绘制Test Key并进行WAT测试验证者优先。

工艺工程师

职责描述：

1. 工艺良率改善与日常维护，保证产品的顺利生产。

2. 撰写工艺相关SOP/Lesson learnt/SPC 等报告。

3. 工艺相关实验执行及其他主管安排事项。

4. 将设备/工艺进行评价和分析，发现异常解决异常

5. 关注生产线上的工艺情况，解决生产过程中已经或可能出现的工艺问题，处理设备和产品的异常问题，维护工艺的稳定性和产品的良率。保证设备运转，提高设备的生产效率。

6. 积极参与各项工艺改善活动，配合产品良率部门，保证产品的质量和良率。

7. 与设备工程师一起，评估新设备的工作情况，保证新设备尽快投入工作。

任职资格：

1.材料、电气、电子、光学、化学、微电子、物理等相关专业

2.英语4级水平及以上

3.能适应轮班/值班工作和穿无尘服工作。

4.具有强烈的责任心和执行力，踏实严谨，良好的沟通协调能力与团队合作精神。

产学研项目工程师

职责描述：

1.根据公司需求，发掘高校院所的技术资源，为公司的生产研发提供支持

2.基于产业化平台，联合高校院所理论和人才优势，解决工厂生产研发问题，负责产学研项目的立项工作

3.紧密沟通工厂各部门以及高校院所，政府部门，推动和管理产学研合作项目

任职资格：

1.微电子、光电子、物理、材料等相关专业，英语6级以上

2.了解半导体器件物理，集成电路制造工艺基本知识

3.具有良好的表达能力，沟通能力

联系方式：

ShanShan_Jin@sticbj.com

Haitong_Yu@sticbj.com

北方集成电路技术创新中心（北京）有限公司招聘简章

公司简介：

北方集成电路技术创新中心（北京）有限公司，是中芯国际集成电路制造有限公司为突破发展制约，聚集产业创新资源，联合国内顶尖集成电路设计、装备、材料及零部件企业共同组建的研发及技术服务平台，是在国家及北京市支持下，为响应国家创新战略而最早成立的集成电路产业创新中心之一。

创新中心立足自主创新，以制造平台为基础，以技术研发为核心，承担“双肩挑”的创新任务，一肩促进“装备、材料及零部件企业的协同发展”，一肩促进“芯片设计企业的做大做强”，致力于建设以产品工艺研发为主要特色的国家级集成电路综合性产业创新中心。创新中心立足国内产业基础，面向全球高等院校，开展以企业为主体的产学研合作，进行国际最前沿的半导体技术研究。

创新中心业务包括与集成电路、半导体有关的芯片制造、技术开发、设计服务、技术服务、技术转让和技术咨询等。

岗位需求：

工艺整合研发工程师

职位描述：

1.本岗位属于12英寸先进工艺技术研发岗位。主要负责集成电路前沿产业技术先导研究及开发，与创新企业及高校研究所合作开展创新成果产业化验证及转化，并在12英寸大规模集成电路生产线上的工艺实现

2.按照项目要求，完成工艺制程（Process）在12英寸厂的建立、开发、优化，最终实现预期结构及电学功能，形成自主性研发成果。主要研究方向：先进逻辑器件及工艺（TFET/GAA/CIS等）、嵌入式新型存储器集成工艺（RRAM/FeRAM等）、先进封装工艺集成（3D/2.5D/Chiplet等）

3.与光罩生产部门、OPC部门合作，沟通新项目所需光罩OPC信息，确保项目layout数据准确制备出光罩

4.与各工艺工程部门密切沟通，建立研发项目所需的工艺流程，设计实验条件，完成流片验证并测试，实现电学功能

5.与产业链上下游合作，推动先进工艺设备、材料、EDA工具的研发

任职资格：

1.微电子、电子、物理、材料、化学等理工科专业

2.英语六级或以上；具有良好的听说读写能力

3.熟练使用PPT, word, excel等office软件

4.有项目研发思维、创新精神；有责任心，团队合作精神

5.具有集成电路工艺生产、研发或器件开发经验者优先

OPC工程师

职位描述：

1.协助尖端产品光学临近效应修正过程从公司研发部门到光罩厂的技术转让研究，包括程式启动设立，程式运转及监控，程式结果分析以及weak point相关的程式纠错。

2.成熟节点光学临近效应修正产品的问题探究和优化处理。

任职资格：

1.光学、微电子等相关专业

2.掌握OPC建模方法

3.了解霍普金斯衍射积分，能够独立进行source优化与mask optimization

工艺整合工程师

职责描述：

1.主导新工艺技术开发流程，包括技术参数制定，工艺流程建立与优化，设计规则制定与验证。

2.对接客户，进行客户风险评估、需求转化，撰写项目立项及研发进度报告。

3.负责已开发平台技术转移，制定技术转移相关工程文件，主导技术转移流程。

4.研发过程中，负责制定工程实验计划、实验晶圆异常情况处理、电性测试程式编写及结果分析，测试结构设计及验证等。

任职资格：

1.微电子类、化工类、物理类、材料类、 数学类等理工科专业。

2.具备良好的沟通能力和团队协作能力。

3.熟悉PN结，BJT，MOSFET等基本半导体器件特性，了解半导体制造基本流程。

4.熟悉刻蚀工艺及设备，熟悉Foundry流片流程，能够绘制Test Key并进行WAT测试验证者优先。

工艺工程师

职责描述：

1. 工艺良率改善与日常维护，保证产品的顺利生产。

2. 撰写工艺相关SOP/Lesson learnt/SPC 等报告。

3. 工艺相关实验执行及其他主管安排事项。

4. 将设备/工艺进行评价和分析，发现异常解决异常

5. 关注生产线上的工艺情况，解决生产过程中已经或可能出现的工艺问题，处理设备和产品的异常问题，维护工艺的稳定性和产品的良率。保证设备运转，提高设备的生产效率。

6. 积极参与各项工艺改善活动，配合产品良率部门，保证产品的质量和良率。

7. 与设备工程师一起，评估新设备的工作情况，保证新设备尽快投入工作。

任职资格：

1.材料、电气、电子、光学、化学、微电子、物理等相关专业

2.英语4级水平及以上

3.能适应轮班/值班工作和穿无尘服工作。

4.具有强烈的责任心和执行力，踏实严谨，良好的沟通协调能力与团队合作精神。

产学研项目工程师

职责描述：

1.根据公司需求，发掘高校院所的技术资源，为公司的生产研发提供支持

2.基于产业化平台，联合高校院所理论和人才优势，解决工厂生产研发问题，负责产学研项目的立项工作

3.紧密沟通工厂各部门以及高校院所，政府部门，推动和管理产学研合作项目

任职资格：

1.微电子、光电子、物理、材料等相关专业，英语6级以上

2.了解半导体器件物理，集成电路制造工艺基本知识

3.具有良好的表达能力，沟通能力

联系方式：

ShanShan_Jin@sticbj.com

Haitong_Yu@sticbj.com

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编辑于 2021-10-27 12:27职场北方芯片（集成电路）​赞同​​添加评论​分享​喜欢​收藏​申请

北方集成电路技术创新中心有限公司2022校园招聘

北方集成电路技术创新中心有限公司2022校园招聘

公司简介

招聘职位

招聘流程

北方集成电路技术创新中心（北京）有限公司，是由集成电路产业链企业共同组建的集成电路及半导体技术相关创新平台，具备北京市产业创新中心，国家高新技术企业资质。

创新中心立足自主创新，以制造平台为基础，以技术研发为核心，承担“双肩挑”的创新任务，一肩促进“产业与科研教学的深度融合”，一肩促进“创新性芯片设计企业的技术转化”，成为以工艺研发为主要特色的国家集成电路技术产业创新中心，推动集成电路产业链纵向整合，聚集发展。创新中心立足国内外产业基础，面向全球高等院校，开展以企业为主体的产学研合作，进行国际最前沿的先进芯片技术研发，围绕集成电路制造领域人才需求，联合培养工程领军人才和专业技术人才，提升集成电路制造产业链整体研发水平。

创新中心业务包括与集成电路、半导体有关的先进芯片技术开发、设计服务、技术服务、技术转让和技术咨询等。

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电影《天才枪手》改编的原案是什么样的？ - 知乎

电影《天才枪手》改编的原案是什么样的？ - 知乎首页知乎知学堂发现等你来答​切换模式登录/注册天才枪手（电影）电影《天才枪手》改编的原案是什么样的？简介都只写到：根据2014年轰动一时的亚洲考场作弊案改编,讲述了天才学霸利用高智商考场作弊牟取暴利的故事。关注者341被浏览754,152关注问题​写回答​邀请回答​好问题 6​3 条评论​分享​7 个回答默认排序蒜香凤梨静物摄影 / 影评创作 /家居美妆/ 产品运营/​ 关注看懂《天才枪手》，你不得不知道的十个问题Q1： 影片的案件原型是什么？A：《天才枪手》的故事是泰国增智高中在STIC考试中l跨大洲作弊，其故事原型是2014年10月到12月，SAT考试亚洲考点接连被爆出考试舞弊，大量考题泄露，该事件涉及几十家教育培训机构，影响包括中国在内的1万余名考生，在教育机构ETS调查作弊案之后，涉案学生均被取消成绩。而在该起作弊案之后两年，2015年至2016年均接连爆出亚洲考生在SAT考试的作弊案。Q2： 片中STIC考试的原型是什么？A：是现实中的SAT考试，SAT考试成绩是世界各国高中生申请美国大学入学资格及奖学金的重要参考，与ACT考试并称为美国高考。与片中STIC考试内容相同，共分为阅读，文法、数学与论文写作四部分。Q3：用时差与考试休息时间作弊具有现实依据吗？A：SAT整场考试共休息3次，分别为阅读和文法之间、第一个数学和第二个数学之间，第二个数学和作文之间；每次休息5分钟。开考时，试卷全部发给学生，但是考试规定每个部分都是限时完成，时间到了必须做后一部分，且不能翻阅前一部分的试题，也不能修改答案。各个考点同一时间开考，存在时差。Q4：为什么片中大规模泰国考生作弊？A：SAT考试分区，在中国仅设香港考点，在亚洲范围内设泰国、日本、新加坡、缅甸、印度等考点，其中尤以香港的监考纪律最严，泰国考点的监考较松，老师的巡视率不高。Q5： 为什么选择澳大利亚为作弊地点？A：澳大利亚横跨东八东十三个时区，东部与西部相差三个小时，因此SAT考试将澳大利亚划入亚洲考点，与亚洲包括泰国在内的所有考点使用同一套试卷，亚洲有许多教育培训机构已经有派遣记忆大师前往澳洲考试并记下答案进行作弊的先例。Q6： 片中天才琳达与富二代小马为什么要前往美国波士顿求学？A：波士顿是美国最古老最有文化价值的城市，全美人口受教育程度最高的城市。讲到波士顿或许不如纽约、洛杉矶这些城市广为人知，但你一定会知道坐落在波士顿的两大世界顶尖名校——哈佛与麻省理工学院。Q7： 为什么片中主人公都热衷留学？A：大家所熟知的是泰国是旅游国家，但同时泰国也是知名的国际教育中心。上世纪五十年代开始，大量国际学校在泰国兴建，当地国际学校主要是英式和美式教育，大量学生在完成高中学业后都会前往美国及欧洲留学。Q8： 增智高中收取高价赞助费现实中确有其事？泰国国际高中的校园环境建设，并有相较普通高中，更为丰富的课程活动，需要消耗大量经费。因此，因此泰国国际高中学费昂贵，水平较高的国际高中每年学费在四万到七万人民币不等（泰铢20万到35万），片中所说赞助费其实是每位学生的申请入校费，入校费的均价达到两万人民币（10万泰铢左右）。Q9： 琳达与班克在SAT考试中所得酬劳有多丰厚？A：截止至13号，泰铢与人民币的汇率是0.198，出身洗衣店家庭的高中生班克在一场考试作弊中获利是两百万泰铢，折合人民币40万元，相当于一个泰国国际学校的教师六年的工资总和。Q10： 片中的高中生为什么频繁提及挂科这个概念？国际高中氛围较普通全日制高中较自由，与国内大学的学考制度相似，以自行选择课程与未来就读专业方向，国际高中的学生大多以出国留学为主要目的，课堂表现、测试，小考都计入最终成绩，科目挂科需要重修，多数国际高中的出国名额有限，需要通过GPA争取。编辑于 2017-10-15 15:36​赞同 1006​​56 条评论​分享​收藏​喜欢收起​HEDOKICarpe Diem​ 关注2014年的SAT泄题事件(SAT全称Scholastic Assessment Test)俗称美国高考，至于详细内容可以去百度“2014年12月6日，在中国，韩国和其他国家的SAT考卷在早些时候已经在网上流出。很多参加12月6日的考生报告，这次考卷就是2014年3月在美国本土考的SAT考卷。”　　“SAT的出题机构College Board和监考机构ETS，通常使用在美国考过的SAT考卷来当作亚洲区的SAT考卷。在亚洲的SAT考生可以通过种种渠道获得这些考题。更夸张的是，某些考试培训机构会派遣人员去美国或者澳大利亚等国家参加SAT考试，然后记住考题，或者干脆非法的偷偷拍下考卷中的内容。这些机构收集到这些考试真题后，再以考试真题原题为噱头，办价格不菲的考试培训班招揽考生，以此谋利。还有一些亚洲考生，他们会通过查阅一个叫做College Confidential的论坛。在这个论坛上，很多考生会在考试后写下自己考到的题目。” 评论区有朋友提到SAT分北美卷和亚太卷 但是事实是澳大利亚考区属于亚洲太平洋地区，用的和亚洲考区同一套亚太卷讲道理前几年很多这种事啊什么雅思托福 利用时差卖题的 卖机经的…btw如果你去关注一些考试大V，基本上每次这种考试完了都会有人投稿考场回忆=======分割线=======二刷归来 良心电影对了...这部电影的恐怖气氛最高点就是ESSAY几个大字跳出来的时候哈哈哈哈………………分割线………………今天三刷归来啦哈哈哈 以上编辑于 2019-02-15 10:50​赞同 150​​42 条评论​分享​收藏​喜欢

Recommendations for diagnosing STIC: a systematic review and meta-analysis | Virchows Archiv

Recommendations for diagnosing STIC: a systematic review and meta-analysis | Virchows Archiv

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Recommendations for diagnosing STIC: a systematic review and meta-analysis

Review and Perspectives

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Published: 01 December 2021

Volume 480, pages 725–737, (2022)

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Recommendations for diagnosing STIC: a systematic review and meta-analysis

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Joep M. A. Bogaerts 

ORCID: orcid.org/0000-0003-0772-67121 na1, Miranda P. Steenbeek2 na1, Majke H. D. van Bommel2, Johan Bulten1, Jeroen A. W. M. van der Laak3, Joanne A. de Hullu2 & …Michiel Simons1 Show authors

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AbstractOur understanding of the oncogenesis of high-grade serous cancer of the ovary and its precursor lesions, such as serous tubal intraepithelial carcinoma (STIC), has significantly increased over the last decades. Adequate and reproducible diagnosis of these precursor lesions is important. Diagnosing STIC can have prognostic consequences and is an absolute requirement for safely offering alternative risk reducing strategies, such as risk reducing salpingectomy with delayed oophorectomy. However, diagnosing STIC is a challenging task, possessing only moderate reproducibility. In this review and meta-analysis, we look at how pathologists come to a diagnosis of STIC. We performed a literature search identifying 39 studies on risk reducing salpingo-oophorectomy in women with a known BRCA1/2 PV, collectively reporting on 6833 patients. We found a pooled estimated proportion of STIC of 2.8% (95% CI, 2.0–3.7). We focused on reported grossing protocols, morphological criteria, level of pathologist training, and the use of immunohistochemistry. The most commonly mentioned morphological characteristics of STIC are (1) loss of cell polarity, (2) nuclear pleomorphism, (3) high nuclear to cytoplasmic ratio, (4) mitotic activity, (5) pseudostratification, and (6) prominent nucleoli. The difference in reported incidence of STIC between studies who totally embedded all specimens and those who did not was 3.2% (95% CI, 2.3–4.2) versus 1.7% (95% CI, 0.0–6.2) (p 0.24). We provide an overview of diagnostic features and present a framework for arriving at an adequate diagnosis, consisting of the use of the SEE-FIM grossing protocol, evaluation by a subspecialized gynecopathologist, rational use of immunohistochemical staining, and obtaining a second opinion from a colleague.

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IntroductionEpithelial ovarian cancer (EOC) is the most lethal gynecological cancer. The most common histological subtype of EOC is high-grade serous carcinoma (HGSC), which is accountable for the majority of EOC deaths [1, 2]. HGSC has a poor prognosis, mainly because it is often diagnosed at an advanced stage. To date, no successful screening tools for early detection of HGSC have been found [3]. Therefore, women who are at an increased risk of developing HGSC are counselled on risk reducing salpingo-oophorectomy (RRSO). This group mainly consists of carriers of BRCA1/2 pathogenic variant (PV), who have a life-time risk of 16–44% to develop EOC [4]. Though RRSO has negative side effects linked to the iatrogenically induced premature menopause, it has proven to be a very successful strategy in order to reduce HGSC risk by 80–96% [5, 6].Our understanding of the pathogenesis of HGSC has greatly improved over the last few decades. Convincing evidence for a precursor lesion, originating in the fallopian tubes, has been found. This precursor lesion is most commonly referred to as serous tubal intraepithelial carcinoma (STIC). Correspondence between TP53 mutations in STIC lesions and in concomitant HGSC provides evidence for a clonal relationship [7]. Moreover, an additional study on telomere length showed that STIC should be considered as a precursor lesion, rather than a non-invasive metastasis of carcinoma [8]. Other aberrant lesions in fallopian tube epithelium have also been identified such as serous tubal intraepithelial lesions (STIL) and p53 signatures. These lesions also contain TP53 mutations, but lack the full cytomorphological and immunophenotypical features of STIC. Sometimes these lesions are grouped together as early serous proliferations (ESP). When these ESP present in an isolated status, no substantial malignant potential has been objectified so far [9]. Examples of STIC, STIL, and p53 signature lesions are shown in Fig. 1.

Fig. 1A: Example of a STIC, with H&E showing aberrant morphology (A-1), p53 overexpression (A-2), and a high Ki-67 labelling index (A-3). B: Example of a STIL, with H&E showing moderately aberrant morphology (B-1), p53 overexpression (B-2), and a low Ki-67 labelling index (B-3). C: Example of a P53 signature, with no aberrant morphology (C-1) p53 overexpression (C-2) and a low Ki-67 labelling index (C-3)Full size imageWith the discovery that precursor lesions to HGSC originate in the fallopian tube, possible alternative preventive strategies for woman at an increased risk of developing HGSC emerge. Such strategies, consisting of a salpingectomy with delayed oophorectomy are currently being studied [10]. To also reduce ovarian cancer risk for low-risk women, an opportunistic salpingectomy can be considered under the appropriate circumstances. This means that the fallopian tubes are removed when a patient undergoes abdominal surgery for another benign indication [11, 12]. Thirteen FIGO (International Federation of Obstetrics and Gynecology) member societies currently have statements regarding opportunistic salpingectomy, whereby a majority support considering this practice [13].STIC diagnosis is very rare for women undergoing salpingectomy for benign indications, (< 0.01%) [14]. In contrast, 11 to 61% of HGSC cases present with a concomitant STIC lesion [15]. Not all cases of HGSC have a clear precursor lesion, for which there may be several reasons. First of all, HGSC is often diagnosed in an advanced stage, whereby the fallopian tube can be obliterated or overgrown with carcinoma. Second, there may be sampling error, or STIC may remain unreported in the pathology report because it has no clinical consequences in the setting of HGSC. A third reason might be found in the “precursor escape” model, presented by Soong et al. They postulated a dual model, where next to STIC, other lesions, such as STIL or p53 signatures, might exfoliate precursor cells onto the ovaries or peritoneal cavity. These exfoliated cells could then, in a later stage, undergo malignant transformation, without leaving remnants of a precursor lesion in the fallopian tube itself [16]. Though the exact pathogenesis of HGSC is not yet fully unravelled, it is clear that the fallopian tube and especially STIC play an important role in it.On the individual patient level, the detection of STIC is important, because it can have implications on prognosis. For example, in the case of RRSO, STIC is related to an increased risk of HGSC of the peritoneum [16, 17]. So far, it is not clear whether the identification of STIC should lead to additional staging and/or chemotherapy [18]. Additionally, reliable STIC diagnosis would be an absolute requirement in the setting of alternative risk reducing strategies. In these studies, the detection of STIC indicates an increased risk for HGSC and would prompt for an immediate oophorectomy [10]. Finally, on a population level, recognizing and adequately classifying STIC and other lesions, such as STIL and p53 signatures, are important in better understanding the oncogenesis of HGSC.Multiple efforts to improve STIC detection have been initiated over the years. Grossing protocols, such as the “Sectioning and Extensively Examining the FIMbriated end” (SEE-FIM) have been developed [19]. Next to that, multiple diagnostic algorithms have been proposed on how to approach a STIC diagnosis, with the aim of assisting the pathologist towards a more consistent diagnosis.Our objective is to set up a systematic review to provide an overview of current practices in the pathological diagnosis “STIC.” We will cover the use of grossing protocols, morphological criteria, training level of the pathologist, and the use of immunohistochemical stains (IHC). Because STIC and its diagnostic approach are commonly best described in studies on RRSO from BRCA1/2-PV carriers, we limited ourselves to these studies.Materials and methodsSearch strategyA literature search strategy was designed for Embase, Medline, and Cochrane (CENTRAL) from inception until 1 September 2020, with search terms for BRCA, risk-reducing surgery, and pathological outcome. Three independent researchers (JBo/MSt/JHe) first screened the studies by title and abstract and secondly by full text. Each study was assessed by at least 2 researchers. Discrepancies were resolved by discussion or consultation of a third researcher (MSi). The review was performed in concordance with a protocol registered in PROSPERO (CRD42020120728). The search protocol is provided in the supplementary appendix.Study selectionAll studies describing the pathology results of a risk-reducing salpingo-oophorectomy, performed among BRCA1/2 PV carriers, aimed at defining the incidence or describing the histopathological characteristics of ovaries and fallopian tubes, were considered eligible for inclusion. Though STIC is also reported in women without a known BRCA1/2 PV, the incidence in this group is low. As the incidence rates will be used to compare the effectiveness of various diagnostic features, this group might form a bias and was therefore excluded. For studies containing only summarized results for BRCA1/2-PV carriers, authors were asked to provide the subgroup data. Articles were excluded if these data remained unavailable. Articles written in another language than English or Dutch, conference abstracts, case reports, and review articles were also excluded.Data extractionThe primary outcomes recorded were incidence of STIC, morphological characteristics, the use of grossing protocols, the use and role of IHC, and whether a subspecialized gynecopathologist assessed the pathology specimens. Secondary outcomes included the incidence of invasive carcinomas hyperplasia, atypia, p53-signatures, and STIL. Sensitivity analyses were performed on the method by which tissue was embedded (not done/unknown, totally embedded, or in conformity with the SEE-FIM protocol), whether a subspecialized gynecological pathologist made the pathological assessment (yes/no/unknown) and on the use of IHC (yes/no/unknown). The authors were contacted in case of missing data or inconsistencies.Risk of bias within studies assessmentThe methodological quality was independently assessed by two review authors (JBo/MSt) according to the standardized quality assessment tool for observational cohort and cross-sectional studies of the National Heart, Lung and Blood institute (NIH). Disagreements were resolved by discussion of consultation of a third review author (MSi).Statistical analysisFor the statistical analysis, with random effect models, and plots, we used R (A language and environment for statistical computing; R Foundation for Statistical Computing, Vienna, Austria, version 4.0.4, packages “meta” and “dplyr”).ResultsStudy selectionThe literature search identified 4133 studies. The selection of studies is displayed in the PRISMA flow diagram, provided in the supplementary appendix (supplement Fig. 1). After removal of 1976 duplicates, the remaining 2157 studies were screened. We excluded 1959 studies based on title and abstract, and another 159 studies were excluded after full-text assessment. A total of 39 studies met the inclusion criteria. A summary of the strengths and weaknesses of study quality is provided in the supplementary appendix (supplement Fig. 2).Study characteristicsThe characteristics of all included studies are shown in Table 1. Studies were published between 2004 and 2020 and consisted of 10 prospective studies and 29 retrospective studies. The 39 studies included in this review collectively reported on 6833 patients, whereby 3642 patients carried a known BRCA1 PV, 2695 patients a BRCA2 PV, and 35 patients both a BRCA1 and BRCA2 PV. For 461 patients, the type of BRCA PV was not specified. The reported incidence of STIC varied between the cohorts and ranged from 0 up to 10% of cases [20]. In a meta-analysis with random effect, a pooled estimated proportion of STIC of 2.8% (95% CI, 2.0–3.7) was found (Fig. 2).

Table 1 Characteristics of the included studiesFull size tableFig. 2Forest plot on the proportion of STIC in included studiesFull size imageOther aberrant epithelial lesions are reported on to a limited extent. The term “hyperplasia” is mentioned in three studies with an estimated incidence of 17.3% (95% CI, 0.0–94.5) [20, 31, 33]. “Atypia” is reported in five studies, with an estimated incidence of 11.0% (95% CI, 2.9–23.3) [20, 21, 28, 31, 33]. P53 signatures are reported on by six studies, with an estimated incidence of 16.2% (95% CI, 2.2–39.7) [16, 20, 25, 27, 40, 47]. Finally, STIL was reported on by six studies and has an estimated incidence of 1.6% (95% CI, 0.3–3.8) [16, 26, 27, 44, 47, 55].Totally embedding and SEE-FIM protocolOut of the 39 studies examined, 20 studies report the consistent use of the SEE-FIM grossing protocol. Fourteen studies report that SEE-FIM was not (always) used, and five studies do not report on the use of a specific grossing protocol. The incidence of STIC in studies applying the SEE-FIM protocol was 2.8% (95% CI, 1.9–3.9), while an incidence of 2.7% (95% CI, 1.3–4.6) was found in studies without the SEE-FIM protocol (p = 0.92) (supplement Fig. 3).Most of the studies did totally embed the risk reducing salpingo-oophorectomy specimens. Apart from the 20 studies who applied the SEE-FIM protocol, an additional 10 studies describe fully embedding all the specimens. This means that the entire fallopian tubes were embedded, but contrary to the SEE-FIM protocol, the fimbriated end was not sectioned parallel to the long axis of the fallopian tube. Out of the remaining nine studies, four studies report not always fully embedding the specimens. For the other five studies, this information was missing. When comparing the group of studies who totally embedded all specimens with the studies who did not, a respective difference in incidence of 3.2% (95% CI, 2.3–4.2) and 1.7% (95% CI, 0.0–6.2) was found (p = 0.24) (Fig. 3).

Fig. 3Forest plot representing the proportion of STIC, with subgroup analysis based on whether all specimens were totally embeddedFull size imageMorphological criteriaA total of 19 studies described the morphological criteria used to identify potential STIC lesions. The most commonly mentioned characteristic was loss of polarity which was mentioned in 15 studies (15/19), followed by nuclear pleomorphism/atypia (13/19), high nuclear to cytoplasmic ratio (13/19), mitotic activity (11/19,) pseudostratification (10/19), prominent nucleoli (10/19), loss of ciliated cells (8 /19), detachment of cells from the surface (3/19), apoptotic bodies (1/19), and abnormal chromatin (1/19). The described morphological criteria used for identifying STIC are shown in Fig. 4.

Fig. 4Morphological criteria attributed to STIC. The x-axis represents the number of studies reporting the criteriaFull size imageSubspecialized pathologistPathology specimens are reported to have been assessed by a subspecialized (or dedicated) gynecopathologist in 25 out of 39 studies. Of the remaining studies, one reported that a general pathologist analyzed the specimens, and 13 studies did not report on this feature. The studies with a reported subspecialized gynecopathologist had a STIC incidence of 3.1% (95% CI, 2.1–4.2), compared to an incidence of 2.3% (95% CI, 1.1–3.9) for the other studies (p = 0.34) (Supplement Fig. 4).ImmunohistochemistryThe use of IHC in diagnosing STIC was described by 21 studies. All these 21 studies performed p53 stainings, and 19 studies used an additional Ki-67 marker. When we compared the studies describing the use of IHC, with those who did not, we saw an equal incidence of STIC in these groups of 2.8%. (95% CI for IHC group 1.6–4.2; 95% CI for unknown group 1.8–4.1). (Supplement Fig. 5). Ten of the studies also commented on the interpretation of IHC. Five studies considered an aberrant p53 staining pattern, either being overexpression or complete loss of expression, combined with an increased proliferative activity (Ki-67), a prerequisite for diagnosing STIC. The other 5 studies described IHC as being supportive, but not necessary for the diagnosis. A table, providing an overview on how these articles describe dealing with IHC, is provided in the supplementary appendix (supplement Fig. 6).DiscussionClinical relevanceIt is essential to reliably diagnose or exclude STIC lesions. Firstly, because safety of novel preventive strategies in trial settings, such as salpingectomy with delayed oophorectomy, for women at high inherited risk for ovarian cancer, depends on STIC assessment. Secondly, because STIC at risk-reducing surgery is associated with increased risk to develop peritoneal carcinomatosis and might indicate for additional staging surgery and treatment, which is currently being debated. In this systematic review and meta-analysis, we provide a framework for diagnosing STIC. We analyzed the use of grossing protocols, the most commonly used morphologic criteria, the training level of pathologists, and the use of IHC.Grossing protocolsSTIC diagnosis starts with a comprehensive grossing protocol. In our meta-analysis, we found a slightly higher detection of STIC when the specimens were fully embedded compared to studies who applied representative sampling. The additional value of the SEE-FIM protocol was not readily apparent in the data, yet makes theoretical sense. STIC is a lesion which is not macroscopically visible. Especially in the setting of risk reducing salpingo-oophorectomy, the lesions can be very small, ranging between < 1 and 11 mm [21, 22, 24, 25, 29, 39, 50]. Therefore, extensive sampling is vital. In addition, it is found that STIC often presents in the fimbriated end of the fallopian tube [19, 58]. In order to optimize the exposure of the distal fallopian tube, the SEE-FIM protocol was developed, which uses longitudinal sectioning of the fimbriated end [19]. The value of this protocol versus representative sampling in the setting of HGSC was demonstrated by Koc et al. They compared the outcomes of 39 cases of HGSC, examined according to the SEE-FIM protocol, with 113 cases, examined by representative sampling. In the SEE-FIM group, they found 15 STIC lesions, compared to 1 STIC lesion in the classic grossing method [59]. The SEE-FIM protocol could also be of added value in gyneco-oncological indication, other than risk reducing salpingo-oophorectomy or HGSC. For example, the International Society of Gynecological Pathologists now recommends to also use the SEE-FIM protocol in patients with endometrial carcinoma, or at least to include the entire fimbrial end [60].Morphologic criteriaThe morphological criteria used in detecting STIC were mentioned by 16 out of the 32 studies we reviewed. The six most frequently mentioned criteria were (1) loss of polarity, (2) nuclear pleomorphism/atypia, (3) high nuclear to cytoplasmic ratio, (4) mitotic activity, (5) pseudostratification, and (6) prominent nucleoli. These criteria were all mentioned by more than half of the studies commenting on morphology. Whether these criteria were equally weighted and if these criteria are a prerequisite for diagnosing STIC remains unclear in these articles.Fallopian tube tissue consists of stromal components which are lined by a predominantly single layer of secretory, ciliated, and intercalated cells. Recognizing epithelium as being aberrant is a cornerstone in the diagnostic process of STIC. However, standardized morphological criteria for STIC are lacking. Moreover, inter observer variability for recognizing aberrant fallopian tube epithelium is found to be high in multiple studies. Carlson et al. asked six pathologists and six pathology trainees to review a total of 30 cases, containing 14 STIC lesions. The majority agreed on 9 out of these 14 cases, leading to a minimal reproducibility, with a kappa (k) score of 0.333 [61]. Visvanathan also only found a weak reproducibility when assessment of STIC was based on morphology alone and found a k-score of 0.39 amongst five pathologists [62]. One can imagine that new technological developments in pathology, such as the use of deep learning algorithms in digitalized H&E slides, may eventually help in this task. Artificial intelligence algorithms have already shown to be able to perform tasks such as fully automated detection of breast cancer metastases in lymph nodes, and automated Gleason grading of prostate biopsies on the level of a subspecialized pathologist [63, 64]. However, for the time being, it is important for both pathologists and clinicians to at least be aware that there is a considerable degree of subjectivity to the morphological interpretation and pathologists are encouraged to seek a second opinion in case of doubt.Training level of the pathologistA slightly higher number of STIC lesions were picked up in studies that explicitly mention that a subspecialized gynecopathologist performed the assessment. It must however be noted that a number of the articles did not clearly comment on whether specimens were seen by a general pathologist or a subspecialized gynecopathologist. One can imagine that a pathologist who works in a centre where there is a research interest in STIC will tend to have an above average expertise on the subject. The true skill level at an average hospital setting, where STIC might only be infrequently encountered in a risk reducing salpingo-oophorectomy setting, therefore remains unclear.The importance of proper training was demonstrated in the difference between trainees and pathologist in Carlson’s study, whereby the agreement between experienced pathologist (k = 0.453) was better than that amongst trainees (k = 0.253) [61]. In addition to the importance of proper training in a general sense, we might ask what the value of a subspecialized pathologist would be in diagnosing STIC. The debate on sub specialization in pathology remains ongoing, whereby the practical downsides must be weighed against the benefits of expanded knowledge and experience [65, 66]. Even though many examinations of fallopian tube specimens could be considered routine work, specialist knowledge and experience may be needed to adequately recognize the special cases.ImmunohistochemistryAdditional IHC staining is often used in diagnosing STIC, most notably p53 and Ki-67. Twenty-one studies mention the use of IHC; however, the remaining studies often did not comment on this. No difference in STIC incidence was found between the group that describes the use of IHC and the one that does not. However, this does not necessarily mean that IHC would not be of added value. IHC stainings might influence the incidence in two ways. On the one hand, IHC may lead to downgrading of cases, e.g., from STIC to STIL. On the other hand, more lesions might be identified due to increased sensitivity. As a result, a comparable incidence may be found regardless of the use of IHC.How these stains are interpreted, either being a prerequisite or a supportive tool, often remains unclear in the articles. Though these stains can indeed prove helpful, we must be aware of how to interpret these stains. Previously suggested diagnostic algorithms often strongly rely on IHC. For example, Visvanathan et al. developed a model based on a combination of morphological suspicion of STIC and the results of p53 and Ki-67 stains [62]. Lesions would subsequently be classified as STIC, STIL, p53 signature, or reactive, based on the combination of these results. An alternative approach was proposed by Meserve et al. who presented a decision tree, starting at identifying altered epithelium and in subsequent steps checking for the presence of cilia, p53 immunostaining pattern, polarity of cells, and finally atypia [67]. The strict application of IHC in these algorithms was already debated by Perrone et al. [68]. They argued that if a lesion is morphologically unequivocally STIC, additional IHC staining can actually be confusing, and that the use of IHC should be reserved for indeterminate cases [68]. Algorithms such as the ones mentioned above can provide a welcome guidance in the diagnostic process, and also seem to improve reproducibility of the diagnosis [69]. There is no harm in using a low-threshold approach for ordering IHC stains, but one should be able to properly interpret these findings and not automatically reject a diagnosis of STIC in case of non-conclusive IHC results.The tumour suppressor gene TP53 has been shown to be mutated in approximately half of all human cancers, in 96.7% of HGSC and in approximately 92% of STIC, tested with TP53 sequencing [10, 70, 71]. In the study from Kuhn et al., only exons 2–9 were sequenced, which will usually be sufficient; however, the actual percentage of STIC, harbouring a p53 mutation, may be higher. Molecular testing for TP53 mutations is the gold standard. However, this is costly, labour intensive, and not always available. IHC can therefore indeed be an attractive substitute for molecular testing. The p53 stain is usually considered to be aberrant, when more than 75% of the nuclei, in a region of at least 12 epithelial cells, show an increased expression, or if there is an complete absence of staining [26, 62]. Kuhn et al. compared IHC staining with genetic testing and found a sensitivity of 87% and a specificity of 100% for IHC. Missense mutations were thereby associated with an overexpression in IHC, and the majority of truncating mutations showed complete loss of staining [7]. Kobel et al. also looked at the accuracy of IHC as a surrogate marker. They tested four different IHC assays for p53 and used next-generation sequencing as gold standard, to test 171 cases of HGSC. The best IHC assay thereby had a sensitivity of 96% and a specificity of 100% [72]. This indicates that IHC may have a high negative predictive value, but there will be a number of false negative cases, varying between 4 and 13%. It is important for the pathologist to be aware that IHC can give false negative results.Additionally, Ki-67 can also play a supportive role in diagnosing STIC; however, the extent to which it can help to distinguish STIC from STIL or reactive lesions remains debatable. Ki-67 is a non-specific proliferation marker. An increased proliferative activity is usually defined as an overall Ki-67 expression of more than 10% of cells, but alternative systems, whereby the maximum proliferative index within a part of the lesion is taken, have also been proposed [12, 69] One of the challenges with Ki-67 however is the high risk of interlaboratory variability. Polley et al. compared staining of 100 breast tissue samples in eight different labs and concluded that cut-off values for Ki-67 for clinical decision making cannot be automatically transferred between laboratories [73].Strength and limitationsThe strength of this review lies in the large number of inclusions, with 39 studies, accounting for a total of 6833 patients. To our knowledge, it is also the first time that these diagnostic features have all been considered in one review. The limitations of this study are found in the predominantly retrospective nature of these studies and the moderate heterogeneity [74]. Varying approaches and insights over time make comparisons of the outcomes of these studies suboptimal. Next to that, the low incidence of STIC and the moderate heterogeneity between studies contribute to insufficient discriminating power. Despite of these limitations, we feel that the collected data provides the best possible current overview on how to approach STIC diagnosis. Further standardization of the diagnostic approach will assist in stronger assessments and research in the future.ConclusionAccurate and reproducible STIC diagnosis is important, both for individual patient care and for better understanding the oncogenesis of HGSC, but remains a challenging task. The diagnostic process can be broken down into several steps, which are highlighted in Fig. 5.

Fig. 5Framework for diagnosing STICFull size imageWe believe that a good grossing protocol, evaluation by a subspecialized pathologist, rational use of immunohistochemical staining, and a low threshold for consultation with a colleague are the building blocks for a proper diagnostic approach toward STIC. Pathologists and clinicians alike should thereby be aware of the sliding scale in various other aberrant lesions, such as STIL and p53 signatures, and the challenges that occur when classifying them. Further standardization of the morphological criteria of STIC, a common approach in the diagnosis of other aberrant lesions in the fallopian tube and a better understanding of their clinical implications is needed.

Data availability

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

Not applicable.

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Download referencesAcknowledgementsWe thank Janoe van Hemert for her contribution in screening articles, Joanna IntHout for supervising the statistical analysis, and the Radboud University Medical Centre’s library for assisting in the retrieval of articles.Author informationAuthor notesJoep M. A. Bogaerts and Miranda P. Steenbeek contributed equally to this workAuthors and AffiliationsDepartment of Pathology, Radboud University Medical Center, Postbus 9101, 6500 HB, Nijmegen, The NetherlandsJoep M. A. Bogaerts, Johan Bulten & Michiel SimonsDepartment of Obstetrics and Gynecology, Radboud University Medical Center, Nijmegen, The NetherlandsMiranda P. Steenbeek, Majke H. D. van Bommel & Joanne A. de HulluDiagnostic Image Analysis Group, Radboud University Medical Center, Nijmegen, The NetherlandsJeroen A. W. M. van der LaakAuthorsJoep M. A. BogaertsView author publicationsYou can also search for this author in

PubMed Google ScholarMiranda P. SteenbeekView author publicationsYou can also search for this author in

PubMed Google ScholarMajke H. D. van BommelView author publicationsYou can also search for this author in

PubMed Google ScholarJohan BultenView author publicationsYou can also search for this author in

PubMed Google ScholarJeroen A. W. M. van der LaakView author publicationsYou can also search for this author in

PubMed Google ScholarJoanne A. de HulluView author publicationsYou can also search for this author in

PubMed Google ScholarMichiel SimonsView author publicationsYou can also search for this author in

PubMed Google ScholarContributionsJBo, MSt, JBu, JdH, and MSi performed study concept and design; JBo and MSt collected the data and wrote the manuscript; JBo, MSt, JL, MB, JBu, JdH, and MSi analyzed and interpreted the data. JL, MB, JBu, JdH, and MSi reviewed and corrected the manuscript. All authors read and approved the final paper.Corresponding authorCorrespondence to

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Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and permissionsAbout this articleCite this articleBogaerts, J.M.A., Steenbeek, M.P., van Bommel, M.H.D. et al. Recommendations for diagnosing STIC: a systematic review and meta-analysis.

Virchows Arch 480, 725–737 (2022). https://doi.org/10.1007/s00428-021-03244-wDownload citationReceived: 16 August 2021Revised: 27 October 2021Accepted: 22 November 2021Published: 01 December 2021Issue Date: April 2022DOI: https://doi.org/10.1007/s00428-021-03244-wShare this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard

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KeywordsBRCA mutationFallopian tubeOvarian carcinomaRisk reducing salpingo-oophorectomySerous tubal intraepithelial carcinoma, STIC

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