摘要
目的总结ROS1(c-ros oncogene1)易位病例分子病理特点及治疗情况;探讨荧光原位杂交(fluorescence in situ hybridization,FISH)技术在肺癌ROS1基因检测中的价值。方法采用荧光原位杂交方法检测613例肺癌患者ROS1基因。ROS1易位样本行手工ROS1免疫组化(IHC)、ALK Ventana全自动免疫组化及EGFR突变检测。结果采用ROS1 FISH法检出19例阳性病例,检出率为3.1%(19/613)。阳性细胞平均比例为60%,范围35%~78%。阳性病例显示两种信号模式,其中63.2%(12/19)为经典红绿分离,36.8%(7/19)为单独绿色。19例阳性病例ROS1蛋白表达为:1例(5%)0+,2例(11%)1+,7例(37%)2+,9例(47%)3+。阳性病例均无ALK基因易位,除1例同时具EGFR 19外显子突变外,其余病例均为EGFR野生型。ROS1易位患者年龄略小;女性、非吸烟患者比例较高;大多为晚期病人。组织学类型以实体、腺泡及乳头型腺癌为主。易位病例中,3例患者死亡,7例患者接受克唑替尼治疗。结论 ROS1易位更易发生在年轻、女性、不吸烟的腺癌患者中。FISH方法可有效地检测肺癌ROS1基因易位,对确诊ROS1阳性肺癌具有重要意义。
Objective To analyze the molecular, pathological, and therapeutic features of ROS1-translocation positive lung cancer cases, and to investigate the value of fluorescence in situ hybridization（FISH）in screening for and confirming the ROS1 translocation. Methods In this study, ROS1-translocation detection was performed in 613 cases with FISH. For ROS1-FISH positive samples, manual ROS1 immunohistochemistry（IHC）, ALK IHC using a Ventana auto-stainer and EGFR mutation status were analyzed. Results 19 ROS1-translocation positive cases were detected by FISH and with a positive incidence of 3.1%. The average percentage of positive tumor cells was 60%, ranging from 35% to 78%. Among these positive cases, 63.2%（12/19） cases displayed classical break apart signals, whereas 36.8%（7/19） showed isolated green signals. In the ROS1-translocation group, the expression of ROS1 protein are as follows： 1 case was not stained 0 ＋（5%）; 2cases had weak expression 1 ＋（11%）; 7 cases had moderate expression 2 ＋（37%） and 9 cases had strong expression 3 ＋（47%）. With the exception of one patient with an EGFR deletion mutation in exon19, ROS1-translocation positive adenocarcinomas in all patients revealed no alterations in ALK or EGFR genes. The ROS1-translocationpositive patients were slightly younger than the negative patients, and were predominantly female,non-smokers. Most of the ROS1-translocation tumors showed solid, acinar and papillary patterns with a more advanced clinical stage. Furthermore, the positive cases all survived except 3 patients, and 7 patients were treated with crizotinib. Conclusion ROS1 rearrangement tends to occur in younger, female, non-smoking lung adenocarcinoma patients. To make a definite positive diagnosis of ROS1-translocationin lung cancer, FISH is a relevant detection method.
作者
陈敏
刘晓羽
吕丽霞
杨洁亮
王威亚
CHEN Min LIU Xiaoyu LV Lixia YANG Jieliang WANG Weiya(Department of Pathology, West China Hospital of Sichuan University, Chengdu, Sichuan, China, 610041)
出处
《分子诊断与治疗杂志》
2017年第2期88-93,共6页
Journal of Molecular Diagnostics and Therapy
基金
国家自然科学基金(81302027)
