作者：胡阿锦，张畅，龚苗子，王云帆，王跃，王淑芳，张雨，缪琦，崔朝丽，张晋夏

单位：北京大学首钢医院 病理科，北京 100144

Authors:  HU Ajin, ZHANG Chang, GONG Miaozi, WANG Yunfan, WANG Yue, WANG Shufang, ZHANG Yu, MIAO Qi, CUI Zhaoli, ZHANG Jinxia

Unit:  Department of Pathology, Shougang Hospital, Peking University, Beijing 100144, China

摘要：

目的   分析CEA、EGFR等肿瘤相关抗原作为CAR-T治疗靶点在结直肠癌中的分布。方法  回顾并选取2014年-2017年的122例结直肠癌病例,应用免疫组织化学法检测肿瘤相关抗原CEA、EGFR、HER2、Mesothelin、MUC1和EpCAM在结直肠癌组织中蛋白表达范围和强度。结果  除HER2 (37.5%)外，其它肿瘤相关抗原在结直肠癌中表达阳性率均在50%以上，EpCAM (100%)、CEA(99.1%)、EGFR(96%)、Mesothelin(67.9%)、MUC1(67%)。CEA(94.6%)和EpCAM(100%)强表达的比例较高，EGFR和Mesothelin分别在10.7%和31.2%的病例中强表达,HER2和MUC1均未见强表达病例。EpCAM(99.1%)、CEA(98.2%)、EGFR(56.2%)在结直肠癌中的表达范围较广(大于50%的肿瘤细胞表达)，Mesothelin和MUC1均灶状表达。除EpCAM外，其它肿瘤相关抗原特异性均较好。仅28.6%的病例共表达 CEA/EGFR/HER2/Mesothelin。64.3%的病例共表达 CEA/EGFR/Mesothelin。其余三抗原共表达的病例均少于50%。高达95.5%的结直肠癌病例共表达CEA/EGFR。除CEA/Mesothelin (67%)及Mesothelin/HER2 (65.2%)外，其余两抗原共表达的病例均少于50%。结论  肿瘤相关抗原CEA和EGFR可作为结直肠癌CAR-T治疗多靶点组合方案的选择。

关键词： 结直肠癌; CAR-T; 肿瘤相关抗原; 免疫组织化学法

Abstract：

Objective  To develop cancer antigen-targeted CAR-T therapeutic strategies for colorectal cancer, we investigated the individual and coexpressions of the tumor-associated antigens CEA, EGFR, HER2, Mesothelin, MUC1 and EpCAM in colorectal cancer. Methods All available hematoxylin and eosin-stained slides from patients who were diagnosed with colorectal cancer (2014-2017) were reviewed. Intensity and distribution for each antigen were assessed by immunohistochemistry in 122 of colorectal cancer cases. Results Positive expression of EpCAM, CEA, EGFR, Mesothelin, MUC1 and HER2 were demonstrated in 100%, 99.1%, 96%, 67.9%, 67% and 37.5% of colorectal cancer cases, respectively. Strong expression of CEA, EpCAM, EGFR and Mesothelin were found in 94.6%, 100%, 10.7% and 31.2% of colorectal cancer cases, while neither HER2 nor MUC1 was strong expression. Distribution≥50% of EpCAM, CEA and EGFR positive tumor cells were observed in 99.1%, 98.2% and 56.2% of colorectal cancer cases, respectively, while both mesothelin and MUC1 were multifocal express in all of colorectal cancer. In addition to EpCAM, specificity of all the other tumor-associated antigens was much better. CEA/EGFR/HER2/Mesothelin was coexpressed in only 28.6% of colorectal cancer cases. Coexpression of CEA/EGFR/Mesothelin was demonstrated in 64.3% of colorectal cancer cases. All the other triple antigen coexpression was demonstrated in less than 50% of colorectal cancer cases. CEA /EGFR were coexpressed in 95.5% of colorectal cancer cases. Except CEA/Mesothelin (67%) and Mesothelin/HER2 (65.2%), the other double antigen coexpression was demonstrated in less than 50% of colorectal cancer cases. Conclusions Tumor-associated antigens CEA and EGFR can be choose for developing multi-targeted CAR-T therapeutic strategies for colorectal cancer patients.

Key Words:  Colorectal cancer; CAR-T; Tumor-associated antigens; Immunohistochemistry