Mesothelin Expression in Advanced Gastroesophageal Cancer Represents a Novel Target for Immunotherapy.
Mesothelin Expression in Advanced Gastroesophageal Cancer Represents a Novel Target for Immunotherapy.
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DOI：
10.1097/pai.0000000000000292
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发表时间：
2016-04
期刊：
影响因子：
--
通讯作者：
Kelly RJ
中科院分区：
文献类型：
--
作者：
Illei PB;Alewine C;Zahurak M;Cowan ML;Montgomery E;Hassan R;Xiang L;Pastan I;Kelly RJ
The identification of new therapeutic targets is of profound importance if we are to improve outcomes in gastro-esophageal cancer. This study assessed the rate of mesothelin expression in tumors of Western patients with upper gastrointestinal tract (GI) carcinomas. In addition, the AGS gastric cancer cell line was tested for sensitivity to SS1(dsFv)PE38, a mesothelin-targeting immunotoxin. Previously constructed tissue microarrays containing samples from 127 patients with gastro-esophageal adenocarcinomas were examined by immunohistochemistry (IHC) for mesothelin expression. Labeling for HER2-neu, E-cadherin and c-Met were also assessed. Tumors were considered positive for mesothelin if at least moderate cytoplasmic/membranous or luminal staining was present in minimum 10% of the neoplastic cells. The AGS gastric cancer cell line was assessed for surface mesothelin expression by flow cytometry and the viability of cells treated with SS1P was measured. Gastroesophageal cancers were mesothelin positive in 64/127 tumors (50.4%, 95% CI: 41.4 to 59.4%) while only 9 carcinomas (7.1%, 95% CI: 3.3 to 13.0%) were Her2-neu IHC 3+ positive and 8 (6.6%, 95% CI: 2.9 to 12.5%) were c-met positive. Mesothelin expression increased from stage I to stage IV tumors (37.5% to 56.3% respectively, p=0.10). The AGS gastric cancer cell line was sensitive to the immunotoxin with an EC50 value in the low picomolar range (0.4 ng/mL). A gastric cancer cell line derived from a Western patient was exquisitely sensitive to the mesothelin-targeted immunotoxin SS1P. Clinical trials involving novel mesothelin targeted immunotherapeutics in gastro-esophageal cancer are currently in development.
