RRC ID 65931
著者 Inaguma S, Wang Z, Lasota J, Onda M, Czapiewski P, Langfort R, Rys J, Szpor J, Waloszczyk P, Okoń K, Biernat W, Ikeda H, Schrump DS, Hassan R, Pastan I, Miettinen M.
タイトル Comprehensive immunohistochemical study of mesothelin (MSLN) using different monoclonal antibodies 5B2 and MN-1 in 1562 tumors with evaluation of its prognostic value in malignant pleural mesothelioma.
ジャーナル Oncotarget
Abstract Mesothelin (MSLN) is a glycophosphatidylinositol (GPI)-linked cell surface protein highly expressed in several types of malignant tumors sometimes in association with increased tumor aggressiveness and poor clinical outcome. In the present study, 1562 tumors were immunohistochemically analyzed for mesothelin expression using two different types of mouse monoclonal antibodies (5B2 and MN-1) to determine the clinical usefulness of mesothelin immunohistochemistry as well as to pinpoint potential targets for future anti-mesothelin therapy. Also, characterization of selected mesothelin-positive tumors was performed by immunohistochemistry and oncogene sequencing. Among the tumors analyzed, the highest frequencies of mesothelin-positivity were detected in ovarian serous carcinoma (90% in 5B2 and 94% in MN-1). Both antibodies showed frequent positivity in pancreatic adenocarcinoma (71% using 5B2 and 87% using MN-1) and malignant pleural mesothelioma (75% using 5B2 and 78% using MN-1). In malignant mesothelioma, overall survival was significantly longer in the cohort of patients with diffuse membranous expression of mesothelin (P < 0.001). Both antibodies showed positive staining in thymic carcinoma (77% in 5B2 and 59% in MN-1), however, no expression was detected in thymoma. No correlation was detected between mesothelin expression and mismatch repair system deficient phenotype or gene mutation (BRAF and RAS) status in gastrointestinal adenocarcinomas. Mesothelin immunohistochemistry may assist the differential diagnosis of thymoma vs. thymic carcinoma as well as prognostication of mesothelioma patients. Our results demonstrate that patients with solid tumors expressing mesothelin could be targeted by anti-mesothelin therapies.
巻・号 8(16)
ページ 26744-26754
公開日 2017-4-18
DOI 10.18632/oncotarget.15814
PII 15814
PMID 28460459
PMC PMC5432294
MeSH Antibodies, Monoclonal Biomarkers, Tumor* Diagnosis, Differential GPI-Linked Proteins / metabolism* Gene Expression Humans Immunohistochemistry Lung Neoplasms / diagnosis Lung Neoplasms / genetics Lung Neoplasms / metabolism* Lung Neoplasms / mortality* Mesothelin Mesothelioma / diagnosis Mesothelioma / genetics Mesothelioma / metabolism* Mesothelioma / mortality* Mesothelioma, Malignant Mutation Pleural Neoplasms / diagnosis Pleural Neoplasms / genetics Pleural Neoplasms / metabolism* Pleural Neoplasms / mortality* Prognosis Survival Analysis
IF 5.168
リソース情報
ヒト・動物細胞 PANC-1(RCB2095)