通过转录组微阵列分析鉴定DAB2和抗酒石酸酸性磷酸酶1作为上皮样间皮瘤的新型阳性免疫组织化学标志物以用于其与肺腺癌的鉴别诊断

Identification of DAB2 and Intelectin-1 as Novel Positive Immunohistochemical Markers of Epithelioid Mesothelioma by Transcriptome Microarray Analysis for Its Differentiation From Pulmonary Adenocarcinoma.

作者信息

Kuraoka Masatsugu, Amatya Vishwa J, Kushitani Kei, Mawas Amany S, Miyata Yoshihiro, Okada Morihito, Kishimoto Takumi, Inai Kouki, Nishisaka Takashi, Sueda Taijiro, Takeshima Yukio

机构信息

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.

出版信息

Am J Surg Pathol. 2017 Aug;41(8):1045-1052. doi: 10.1097/PAS.0000000000000852.

DOI:10.1097/PAS.0000000000000852

PMID:28394802

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.

摘要

由于目前尚无用于明确诊断恶性上皮样间皮瘤的绝对免疫组化阳性标志物，因此，鉴定可能有助于该诊断的其他“阳性”标志物具有临床重要性。因此，本研究的目的是鉴定恶性间皮瘤的新型阳性标志物。使用从上皮样间皮瘤和肺腺癌的福尔马林固定石蜡包埋组织切片中提取的RNA进行全基因组基因表达分析。基因表达分析显示，与肺腺癌相比，失活同源物2（DAB2）和Intlectin-1在上皮样间皮瘤中的表达明显更高。通过对肿瘤组织RNA进行逆转录聚合酶链反应验证了DAB2和Intlectin-1的mRNA表达增加，并通过对5种间皮瘤细胞系进行蛋白质印迹验证了蛋白质表达。通过对75例上皮样间皮瘤和67例肺腺癌进行免疫组化研究，检测了DAB2和Intlectin-1在上皮样间皮瘤与肺腺癌鉴别诊断中的效用。上皮样间皮瘤中DAB2和Intlectin-1表达的阳性率分别为80.0%和76.0%，肺腺癌中分别为3.0%和0%。免疫组化结果显示，DAB2区分上皮样间皮瘤与肺腺癌的敏感性和特异性分别为80%和97%，Intlectin-1的敏感性和特异性分别为76%和100%。总之，DAB2和Intlectin-1是新鉴定的间皮瘤阳性标志物，有潜力纳入未来用于区分上皮样间皮瘤与肺腺癌的免疫组化标志物组合中。