title: Identification of DAB2 and Intelectin-1 as Novel Positive Immunohistochemical Markers of Epithelioid Mesothelioma by Transcriptome Microarray Analysis for Its Differentiation From Pulmonary Adenocarcinoma.
abstract: As there are currently no absolute immunohistochemical positive markers for the definite diagnosis of malignant epithelioid mesothelioma, the identification of additional "positive" markers that may facilitate this diagnosis becomes of clinical importance. Therefore, the aim of this study was to identify novel positive markers of malignant mesothelioma. Whole genome gene expression analysis was performed using RNA extracted from formalin-fixed paraffin-embedded tissue sections of epithelioid mesothelioma and pulmonary adenocarcinoma. Gene expression analysis revealed that disabled homolog 2 (DAB2) and Intelectin-1 had significantly higher expression in epithelioid mesothelioma compared with that in pulmonary adenocarcinoma. The increased mRNA expression of DAB2 and Intelectin-1 was validated by reverse transcriptase polymerase chain reaction of RNA from tumor tissue and protein expression was validated by Western blotting of 5 mesothelioma cell lines. The utility of DAB2 and Intelectin-1 in the differential diagnosis of epithelioid mesothelioma and pulmonary adenocarcinoma was examined by an immunohistochemical study of 75 cases of epithelioid mesothelioma and 67 cases of pulmonary adenocarcinoma. The positive rates of DAB2 and Intelectin-1 expression in epithelioid mesothelioma were 80.0% and 76.0%, respectively, and 3.0% and 0%, respectively, in pulmonary adenocarcinoma. Immunohistochemically, the sensitivity and specificity of DAB2 was 80% and 97% and those of Intelectin-1 were 76% and 100% for differentiation of epithelioid mesothelioma from pulmonary adenocarcinoma. In conclusion, DAB2 and Intelectin-1 are newly identified positive markers of mesothelioma and have potential to be included in future immunohistochemical marker panels for differentiation of epithelioid mesothelioma from pulmonary adenocarcinoma.
authors.affiliation: Departments of *Pathology ‡Surgery, Institute of Biomedical and Health Sciences ∥Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University †Department of Clinical Research and Laboratory, Hiroshima Prefectural Hospital #Pathologic Diagnostic Center Inc., Hiroshima, Japan ¶Department of Internal Medicine, Okayama Rosai Hospital, Okayama, Japan §Department of Pathology and Clinical Pathology, South Valley University, Qena, Egypt.
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Kuraoka
authors.forename: Vishwa J
authors.initials: VJ
authors.lastname: Amatya
authors.forename: Kei
authors.initials: K
authors.lastname: Kushitani
authors.forename: Amany S
authors.initials: AS
authors.lastname: Mawas
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Miyata
authors.forename: Morihito
authors.initials: M
authors.lastname: Okada
authors.forename: Takumi
authors.initials: T
authors.lastname: Kishimoto
authors.forename: Kouki
authors.initials: K
authors.lastname: Inai
authors.forename: Takashi
authors.initials: T
authors.lastname: Nishisaka
authors.forename: Taijiro
authors.initials: T
authors.lastname: Sueda
authors.forename: Yukio
authors.initials: Y
authors.lastname: Takeshima
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000230:Adenocarcinoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor / Q000032:analysis; D002454:Cell Differentiation; D016207:Cytokines / Q000235:genetics*; D058851:GPI-Linked Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D037102:Lectins / Q000235:genetics*; D008175:Lung Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology*; D008654:Mesothelioma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology*; D000086002:Mesothelioma, Malignant; D046228:Microarray Analysis; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; D016207:Cytokines; C102885:DAB2 protein, human; D058851:GPI-Linked Proteins; C432397:ITLN1 protein, human; D037102:Lectins; D025521:Tumor Suppressor Proteins