二代测序技术揭示宫颈小细胞神经内分泌癌的复发性体细胞突变

免疫组化抗体神器

好评必备! 免费下载

   --本文经《美国外科病理学杂志》授权发布,其他媒体转载或引用须经《美国外科病理学杂志》同意,否则追究法律责任。

  宫颈小细胞神经内分泌癌(small cell neuroendocrine carcinoma,SCNEC)是一种罕见但高度恶性的肿瘤。虽然高危人乳头瘤病毒(human papillomavirus,HPV)参与许多肿瘤的早期发生阶段,但人们也推测某些其他驱动因子也促进了SCNEC的发展。认识这些致癌因子能够指导肿瘤的靶向治疗。本文报道10例宫颈SCNEC的临床病理特征。利用免疫组织化学方法分析pl6、p53、突触素和嗜铬粒蛋白的表达状况;原位杂交和聚合酶链反应技术评估高危HPV和/或HPV18,以及基于637个组合基因的二代测序技术来检测突变的基因。患者年龄从28岁到68岁不等(平均,45.6岁;中位数,40.5岁)。结果发现,所有肿瘤组织均有pl6和突触素的弥漫性表达。除1例外,嗜铬粒蛋白在其他肿瘤组织内都呈阳性(从局灶性到弥漫性不等)。在6例肿瘤组织中检测到HPV18,而只有1例发现有HPV35阳性。在8例肿瘤组织发现至少1例有驱动因子突变,4例患者检测到有TP53体细胞突变,其中3例伴有异常的p53免疫染色;在3例肿瘤中检测到4个P1K3CA突变(p.G106A、p.N345T、p.E545K和p.E545D),其中2例也伴有TP53基因突变;在4例肿瘤组织内检测到涉及KRAS、Erbb2、c-Myc,NOTCH1、SCL6或NCOA3的肿瘤驱动基因突变,它们也通常伴有抑制因子PTEN、RB1、BRCA1、BRCA2和AR1D1B的突变,从而共同引起肿瘤性病变。靶向二代测序技术检测发现SCNEC的MAPK、PI3K/AKT/mTOR和TP53/BRCA 遗传信号传导途径发生变化。这为SCNEC这种高度恶性肿瘤的个体化靶向治疗提供了可行性。
  AmJSurg Pathol 2018;42:750.760
  美国外科病理学杂志中文版2019年第一期摘要NO.5
  沈士亮翻译/审校
  The American Journal of Surgical Pathology中文版声明:
  ©2018 Wolters Kluwer Health
  The material is published by Wolters Kluwer Health with the permission of American Journal of Surgical Pathology.No part of this publication may be reproduced in any form,stored in a retrieval system or transmitted in any form,by any means,without prior written permission from Wolters Kluwer Health.Opinions expressed by the authors and advertisers are not necessarily those of the American Journal of Surgical Pathology, its affiliates,or of the Publisher.The American Journal of Surgical Pathology,its affiliates,and the Publisher disclaim any liability to any party for the accuracy,completeness,efficacy,or availability of the material contained in this publication (including drug dosages) or for any damages arising out of the use or non-use of any of the material contained in this publication.
  Although advertising material is expected to conform to ethical (medical) standards,inclusion in this publication does not constitute a guarantee or endorsement of the quality or value of such product or of the claims made of it by its manufacturer.
 
  【本文经《美国外科病理学杂志》授权发布,其他媒体转载或引用须经《美国外科病理学杂志》同意 ,否则追究法律责任;所有文章仅供公益交流,不代表本站立场。欢迎提供素材、资料等,投稿邮箱: tougao@91360.com,一经采纳将给予稿费】
责任编辑: xuehan
0 0 0

扫一扫下载91360客户端