Cancer antigen profiling for malignant pleural mesothelioma immunotherapy: expression and coexpression of mesothelin, cancer antigen 125, and Wilms tumor 1.
Cancer antigen profiling for malignant pleural mesothelioma immunotherapy: expression and coexpression of mesothelin, cancer antigen 125, and Wilms tumor 1.
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DOI：
10.18632/oncotarget.20845
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发表时间：
2017-09-29
期刊：
影响因子：
--
通讯作者：
Adusumilli PS
中科院分区：
文献类型：
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作者：
Eguchi T;Kadota K;Mayor M;Zauderer MG;Rimner A;Rusch VW;Travis WD;Sadelain M;Adusumilli PS
为了开发针对恶性胸膜间皮瘤（MPM）的癌抗原靶向免疫治疗策略，我们研究了上皮样和非上皮样MPM中癌相关抗原间皮素（MSLN）、癌抗原125（CA 125）和Wilms肿瘤1（WT 1）的单独和共表达。审查了诊断为MPM（1989-2010）的患者的所有可用苏木精和伊红染色切片。我们构建了283例患者的组织微阵列（上皮样= 234;非上皮样= 49）。通过免疫组织化学评估每种抗原的强度和分布。MSLN、CA 125和WT 1在上皮样MPM中的阳性表达率分别为93%、75%和97%，在非上皮样MPM中的阳性表达率分别为57%、33%和98%。三重和双阳性抗原共表达分别在72%和23%的上皮样MPM病例和29%和33%的非上皮样MPM病例中被证明。在<2%的MPM病例中证明了所有三种抗原的表达完全缺失。超过三分之二的MPM病例的MSLN阳性细胞分布≥50%，在其余三分之一中，一半病例的WT 1阳性细胞分布≥50%。CA 125/MSLN共表达在超过三分之二的上皮样MPM病例和三分之一的非上皮样MPM病例中观察到。有限数量的癌症相关抗原可以靶向几乎所有的MPM肿瘤进行免疫治疗。
To develop cancer antigen-targeted immunotherapeutic strategies for malignant pleural mesothelioma (MPM), we investigated the individual and coexpressions of the cancer-associated antigens mesothelin (MSLN), cancer antigen 125 (CA125), and Wilms tumor 1 (WT1) in both epithelioid and non-epithelioid MPM. All available hematoxylin and eosin-stained slides from patients who were diagnosed with MPM (1989-2010) were reviewed. We constructed tissue microarrays from 283 patients (epithelioid = 234; non-epithelioid = 49). Intensity and distribution for each antigen were assessed by immunohistochemistry. Positive expression of MSLN, CA125, and WT1 were demonstrated in 93%, 75%, and 97% of epithelioid MPM cases, and 57%, 33%, and 98% of non-epithelioid MPM cases, respectively. Triple- and double-positive antigen coexpressions were demonstrated in 72% and 23% of epithelioid MPM cases and 29% and 33% of non-epithelioid MPM cases, respectively. Complete absence of expression for all three antigens was demonstrated in <2% of MPM cases. More than two-thirds of MPM cases had ≥50% distribution of MSLN-positive cells and, among the remaining third, half had ≥50% distribution of WT1-positive cells. CA125/MSLN coexpression was observed in more than two-thirds of epithelioid MPM cases and one-third of non-epithelioid MPM cases. A limited number of cancer-associated antigens can target almost all MPM tumors for immunotherapy.