同样的组织病理,为什么生存期大不相同?

2016-06-20 佚名 医谷

《2016世界卫生组织(WHO)中枢神经系统肿瘤分类》首次针对CNS肿瘤在组织学分型基础上增加了分子分型来分类。从而建立了分子时代CNS肿瘤诊断的新概念,神经胶质瘤作为最常见的原发性中枢神经系统肿瘤,分子分型对其诊断治疗有着很重要的意义。          以下是北京协和医院神经外科提供的两例病例,分子病理


《2016世界卫生组织(WHO)中枢神经系统肿瘤分类》首次针对CNS肿瘤在组织学分型基础上增加了分子分型来分类。从而建立了分子时代CNS肿瘤诊断的新概念,神经胶质瘤作为最常见的原发性中枢神经系统肿瘤,分子分型对其诊断治疗有着很重要的意义。
        
以下是北京协和医院神经外科提供的两例病例,分子病理在患者的鉴别诊断、临床分型、预后判断及治疗选择都起到了重要作用。

分子病理诊疗与传统病理有哪些区别和联系?

        
文斌:我举两个病人的例子,一位是2007年入院治疗的53岁男性,已有半年时间的记忆力下降状况,并于入院前3天内伴随突发剧烈头痛,术前CT可见点状钙化灶,术后组织病理显示是WHO Ⅲ级的脑胶质瘤(间变少突胶质细胞瘤)。紧接着我们为他做了分子病理检测,发现他有三项指标阳性:MGMT启动子区甲基化、IDH基因突变、以及1p/19q染色体联合缺失。这些分子指标提示,患者对放化疗敏感,而且生存期较长。后来我们对患者进行放疗+辅助化疗,效果非常好,患者至今仍处于病情稳定状态。
        
另一个例子就不那么令人喜悦,是2015年入院的一位43岁女性,入院前已有9个月的阵发性恐惧感及两周的乏力和恶心症状,术后组织病理显示,同样是WHO Ⅲ级的脑胶质瘤(间变性星形少突细胞瘤)。我们同样为她做了分子病理检测,发现上述刚提到的三项指标均为阴性,TERT基因启动子区突变,这一指标阳性。这提示患者对放化疗不敏感,且病程进展迅速,生存期较短。后来同步放化疗一个月后,果然在术后四个月时患者病灶复发,2疗程辅助化疗后,术后六个月时患者头痛开始加重。
        
从这两个例子我们能看出,分子病理对疾病的鉴别诊断、临床分型、预后判断、治疗选择等,都有非常重要的意义。今年,目前国际权威指南《2016世界卫生组织(WHO)中枢神经系统肿瘤分类》也首次针对CNS肿瘤在组织学分型基础上增加了分子分型来分类,从而建立了分子时代CNS肿瘤诊断的新概念。

提到的其他分子标志物又有哪些作用呢?

        
马文斌:MGMT启动子区甲基化:可预测III、IV级胶质瘤患者是否能从烷化剂化疗中获益;1p19q联合缺失:可将有无 1p19q 染色体杂合性联合缺失作为评估低级别胶质瘤风险级别的指标之一,并将其作为III级间变性胶质瘤分型的标志物。携带1p19q联合缺失的胶质瘤形态学通常为少突胶质细胞瘤,预后较良好,具有更长的生存期,并对放疗和化疗都比较敏感;
        
IDH1/2基因突变和TERT启动子点突变:IDH基因和TERT基因的作用就更多了,可将有无 IDH1/2 基因突变作为评估低级别胶质瘤风险级别的指标之一。携带IDH1/2突变的患者为低风险。
        
IDH1/2和TERT启动子区点突变联合定义了胶质瘤的分子分型
        
其用于预后:只携带TERT突变的IV级胶质母细胞瘤(原发)或III级间变性胶质瘤,预后不良;只携带IDH1/2突变的胶质瘤多呈现星形细胞形态,生存期较长;同时携带TERT和IDH1/2突变的胶质瘤多呈现少突神经细胞形态,预后最为良好。
       
其用于治疗:IDH突变的恶性星形胶质细胞瘤患者更适合手术切除,且全切除可延长生存期(neuro-oncology 2013);IDH突变的胶质母细胞瘤同步放化疗疗效优于无IDH突变的胶质母细胞瘤(neuro-oncology 2014);
        
潜在药物:包括胶质瘤在内携带IDH1突变的高级别实体瘤受试者口服AG-120临床研究(clinicaltrial.gov);携带IDH1突变的复发II级胶质瘤患者入组肿瘤特异性肽疫苗的安全性和免疫原性研究(clinicaltrial.gov)。

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    2016-10-11 ylzr123

    拜读了,受益匪浅,点个赞!

    0

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    2016-09-01 李东泽

    很好,不错,以后会多学习

    0

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    2016-08-27 李东泽

    这篇资讯带给我们新知识,启发新思维,不论是科研还是临床工作都有很大的帮助。。。

    0

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    2016-06-27 微分

    免疫分型很重要

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=146177, encodeId=63291461e77d, content=拜读了,受益匪浅,点个赞!, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7s7ZCKOmmbBTD6nE7gcd5OZpvyGEzkxBP3S275k5ZJVrsPkotZhBglRHM9rKvcj1OgkssqhcnoPw8zIaMZTF8c/0, createdBy=4c441942088, createdName=ylzr123, createdTime=Tue Oct 11 22:51:01 CST 2016, time=2016-10-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=108863, encodeId=21e81088637e, content=很好,不错,以后会多学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzUn81b5CF5ibVPib8jWI92iciaxmqGHlwruOnK4SVZykd4iahqo1hicklIibyZoxm55X7EM8BW9eX1h1hQ2/0, createdBy=8aa81937526, createdName=李东泽, createdTime=Thu Sep 01 12:58:00 CST 2016, time=2016-09-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=105576, encodeId=486f1055e6cd, content=这篇资讯带给我们新知识,启发新思维,不论是科研还是临床工作都有很大的帮助。。。, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzUn81b5CF5ibVPib8jWI92iciaxmqGHlwruOnK4SVZykd4iahqo1hicklIibyZoxm55X7EM8BW9eX1h1hQ2/0, createdBy=8aa81937526, createdName=李东泽, createdTime=Sat Aug 27 14:23:00 CST 2016, time=2016-08-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=91335, encodeId=2e4b9133584, content=免疫分型很重要, beContent=null, objectType=article, channel=null, level=null, likeNumber=159, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a6831717982, createdName=微分, createdTime=Mon Jun 27 15:34:00 CST 2016, time=2016-06-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1378101, encodeId=718313e810176, content=<a href='/topic/show?id=c29b69004f9' target=_blank style='color:#2F92EE;'>#生存期#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=69004, encryptionId=c29b69004f9, topicName=生存期)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8e886, createdName=仁者大医, createdTime=Wed Jun 22 04:48:00 CST 2016, time=2016-06-22, status=1, ipAttribution=)]

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