肺浸润性黏液腺癌与混合性浸润性黏液-非黏液腺癌的临床病理学分析  

Invasive mucinous adenocarcinoma of the lungs versus mixed invasive mucinous andnon-mucinous adenocarcinoma: a clinicopathological analysis

作　　者：彭双双 李微[1] 周照雅 张标[1] 王朝姗 濮晓红 杨雯 杨军[1] 吴鸿雁[1] 付尧[1] 陈洁宇[1] 樊祥山[1,3] PENG Shuangshuang;LI Wei;ZHOU Zhaoya;ZHANG Biao;WANG Chaoshan;PU Xiaohong;YANG Wen;YANG Jun;WU Hongyan;FU Yao;CHEN Jieyu;FAN Xiangshan(Department of Pathology,Nanjing Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing University,Nanjing 210008,China;Department of Pathology,Nanjing Jiangbei Hospital,Nanjing 210044,China;Department of Pathology,Nanjing Drum Tower Hospital,Clinical College of Nanjing Medical University,Nanjing 210008,China;Department of Imaging,Nanjing Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing University,Nanjing 210008,China)

机构地区：[1]南京大学医学院附属鼓楼医院病理科,南京210008 [2]南京江北医院病理科,南京210044 [3]南京医科大学鼓楼临床医学院病理科,南京210008 [4]南京大学医学院附属鼓楼医院影像科,南京210008

出　　处：《临床与实验病理学杂志》2023年第11期1328-1333,共6页Chinese Journal of Clinical and Experimental Pathology

摘　　要：目的探讨肺浸润性黏液腺癌(invasive mucinous adenocarcinoma,IMA)与混合性浸润性黏液-非黏液腺癌(mixed invasive mucinous and non-mucinous adenocarcinoma,mIMA)的临床病理学特征、诊断及鉴别诊断。方法收集36例肺原发IMA和17例mIMA患者的临床资料,采用免疫组化EnVision两步法检测TTF-1、CK7、CK20、SATB2、CDX2、EGFR、HNF4a等蛋白的表达。应用Sanger法和FISH法检测KRAS突变和NRG1基因重排,分析其临床病理学特征并复习相关文献。结果IMA中有9例(25.0%)有乳头结构、3例(8.3%)有微乳头结构,mIMA中13例(76.5%)有乳头结构(P<0.001)、9例(52.9%)有微乳头结构(P=0.001)。IMA高核级5例(13.9%),mIMA高核级10例(58.8%)(P=0.002)。TTF-1在IMA中阳性率为37.5%,其在mIMA黏液腺癌和非黏液腺癌成分中阳性率分别为60.0%、80.0%(P=0.021)。CK7、CK20、CDX2在IMA中阳性率为90.6%、21.9%、9.4%,三者在mIMA黏液腺癌和非黏液腺癌成分中阳性率分别为100%、20%、20%和100%、6.7%、6.7%,SATB2均不表达。总EGFR和两种EGFR突变特异性抗体(L858R、DEL19)在IMA、mIMA中的表达差异无统计学意义。mIMA中有3例黏液腺癌L858R阳性,其中2例非黏液腺癌阴性;另有1例mIMA非黏液腺癌成分DEL19阳性,其在黏液腺癌中阴性。IMA中HNF4a的阳性率为72.0%(18/25),mIMA黏液腺癌和非黏液腺癌成分中HNF4a阳性率分别为41.7%(5/12)、33.3%(4/12)(P=0.048)。19例IMA行基因测序有9例(47.4%)KRAS突变,以G12D、G12V最为常见。4例mIMA行基因测序,均未显示KRAS突变。FISH检测示2例(7.1%)IMA有NRG1易位重排。结论肺mIMA比IMA更具侵袭性,mIMA中乳头、微乳头结构、高核级的病例显著多于IMA;两者在免疫表型、KRAS突变方面,差异均有统计学意义。Purpose To investigate the clinicopathological characteristics,diagnosis,and differential diagnosis of invasive mucinous adenocarcinoma(IMA)and mixed invasive mucinous and non-mucinous adenocarcinoma(mIMA).Methods The clinical data were collected in 36 patients with primary IMA and 17 patients with mIMA,and the expression of TTF-1,CK7,CK20,SATB2,CDX2,EGFR,HNF4a,etc.was detected by immunohistochemical EnVision two-step method.The Sanger sequencing and the FISH were used for KRAS mutation and NRG1 gene rearrangement detection.The clinicopathological characteristics were analyzed with review of relevant literature.Results There were 9 cases(25.0%)and 3(8.3%)cases of papillary and micropapillary structures in IMA,while 13 cases(76.5%)(P<0.001)and 9 cases(52.9%)(P=0.001)were present in mIMA.There were 5 cases(13.9%)of high nuclear grade of IMA and 10 cases(58.8%)of high nuclear grade of mIMA(P=0.002).TTF-1 had a positive rate of 37.5%in IMA,but 60.0%and 80.0%in the mucinous adenocarcinoma and non-mucinous adenocarcinoma components of mIMA(P=0.021),respectively.The positive rates of CK7,CK20,and CDX2 in IMA were 90.6%,21.9%,and 9.4%,and the positive rates in mucinous adenocarcinoma and non-mucinous adenocarcinoma components of mIMA were 100%,20%,20%and 100%,6.7%,6.7%,respectively and no SATB2 expression was found in all cases.There was no significant difference in the expression of total EGFR and two EGFR mutation-specific antibodies(L858R,DEL19)between IMA and mIMA.There were 3 cases of mucinous adenocarcinoma with L858R positive in mIMA,and 2 of them were negative for non-mucinous adenocarcinoma.In another case,the non-mucinous adenocarcinoma component of mIMA expressed DEL19,but the mucinous adenocarcinoma component was not expressed.The positive rate of HNF4a in IMA was 72.0%(18/25),and those of HNF4a in mucinous adenocarcinoma and non-mucinous adenocarcinoma in mIMA were 41.7%(5/12)and 33.3%(4/12),respectively(P=0.048).KRAS gene sequencing was carried out in 19 cases of IMA,among which 9 cases(47.4%)had mutations,

关 键 词：肺肿瘤 黏液腺癌 FISH 免疫组织化学 KRAS NRG1 

分 类 号：R734.2[医药卫生—肿瘤]