伴食管腺导管分化的食管癌临床病理特征与全外显子组测序分析  

Esophageal carcinoma with ductal differentiation of esophageal gland:clinicopathological characteristics and whole exome sequencing analyses

作　　者：朱珠 胡啸 王正洋 李佳静 王丰[3] 秦慧[3] 简翔宇 李文才[3] 马怡晖[3] Zhu Zhu;Hu Xiao;Wang Zhengyang;Li Jiajing;Wang Feng;Qin Hui;Jian Xiangyu;Li Wencai;Ma Yihui(Department of Biological Sample Bank,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450000,China;Academy of Medical Science,Zhengzhou University,Zhengzhou 450000,China;Department of Pathology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450000,China)

机构地区：[1]郑州大学第一附属医院生物样本库,郑州450000 [2]郑州大学医学科学院,郑州450000 [3]郑州大学第一附属医院病理科,郑州450000

出　　处：《临床与实验病理学杂志》2025年第3期291-297,共7页Chinese Journal of Clinical and Experimental Pathology

基　　金：国家自然科学基金(81900791、82100929);河南省科技攻关项目(192102310322、202102310449)。

摘　　要：目的根据全外显子组测序技术分析伴食管腺导管分化的食管癌体细胞突变特征、关键驱动突变基因和高频突变基因,探讨伴食管腺导管分化的食管癌临床病理特征和免疫表型。方法回顾性分析9例伴食管腺导管分化食管癌的临床病理特征,采用免疫组化EnVision两步法染色,并对其中3例样本行全外显子组测序和数据分析。结果9例患者中男性6例,女性3例;平均年龄68.3岁(61~80岁);9例均位于食管中下段,肿瘤最大径1.5~3.5 cm。镜下肿瘤大部分区域具有双层上皮结构,包含内层腔面上皮与外层基底上皮,局灶癌组织可见角化和黏液细胞。双层上皮的内层腔面上皮CK7阳性,外层基底样上皮p63均阳性。癌组织中S-100、SOX10、c-myb均阴性,p53呈突变型(弥漫强阳性)。全外显子组测序分析显示体细胞突变特征:单核苷酸变异(single nucleotide variant,SNV)数目为796个、片段的插入和缺失(insertion and deletion,InDel)数目为37个和CNV数量482个,关键驱动突变基因12个和高频突变基因TP53。9例鳞状上皮均未见上皮内瘤变,无巴雷特食管或异位胃黏膜。平均随访时间21.9个月(8天~51个月),其中8例存活,1例术后8天因严重肺部感染死亡。结论伴导管分化的食管癌是一种罕见的食管上皮源性恶性肿瘤,具有独特的形态学、免疫表型和分子改变特点。Purpose To summarize the clinical pathological and immunohistochemical characteristics of esophageal carcinoma with ductal differentiation of esophageal gland,and analyze the somatic mutation characteristics,key driving mutation genes,and significantly mutated genes based on whole exome sequencing.Methods The clinicopathological features of 9 cases of esophageal carcinoma with esophageal duct differentiation were retrospectively analyzed,and the immunohistochemistry EnVision two-step method was used to stain them,and 3 of the samples were subjected to whole exome sequencing and data analysis.Results Among the 9 patients,6 were males and 3 were females.The average age was 68.3 years old(61-80 years old).All 9 cases were located in the middle-lower segment of the esophagus.The diameter of the lesion was from 1.5 cm to 3.5 cm.Most areas of the tumor had a double-layer epithelial structure,including the inner layer of luminal epithelium and the outer layer of basal epithelium.Focal areas could be seen with keratinization and mucinous cells.Immunohistochemistry showed that CK7 was positive in the inner epithelium,while p63 was positive in the outer basal epithelium.S-100,SOX10 and c-myb were all negative,and p53 was mutated(diffuse strongly positive).The results of whole exome sequencing analysis showed somatic mutation characteristics(796 SNV,37 InDel,482 CNV),key driving mutation genes(12),and significantly mutated genes(TP53).No intraepithelial neoplasia was observed on the surface squamous epithelium of all cases,and no Barrett’s esophagus or ectopic gastric mucosa was observed.The average follow-up time was 21.9 months(8 days-51 months),with 8 cases surviving and 1 case dying of severe pulmonary infection 8 days after surgery.Conclusion Esophageal carcinoma with ductal differentiation of esophageal gland is a rare epithelial derived malignant tumor of the esophagus,characterized by unique morphological,immunohistochemical,and molecular changes.

关 键 词：食管肿瘤 伴食管腺导管分化 全外显子组测序 形态学 免疫组织化学 

分 类 号：R735.1[医药卫生—肿瘤]