Specific Expression of Human Intelectin-1 in Malignant Pleural Mesothelioma and Gastrointestinal Goblet Cells

PLOS ONE, Dec 2019

Malignant pleural mesothelioma (MPM) is a fatal tumor. It is often hard to discriminate MPM from metastatic tumors of other types because currently, there are no reliable immunopathological markers for MPM. MPM is differentially diagnosed by some immunohistochemical tests on pathology specimens. In the present study, we investigated the expression of intelectin-1, a new mesothelioma marker, in normal tissues in the whole body and in many cancers, including MPM, by immunohistochemical analysis. We found that in normal tissues, human intelectin-1 was mainly secreted from gastrointestinal goblet cells along with mucus into the intestinal lumen, and it was also expressed, to a lesser extent, in mesothelial cells and urinary epithelial cells. Eighty-eight percent of epithelioid-type MPMs expressed intelectin-1, whereas sarcomatoid-type MPMs, biphasic MPMs, and poorly differentiated MPMs were rarely positive for intelectin-1. Intelectin-1 was not expressed in other cancers, except in mucus-producing adenocarcinoma. These results suggest that intelectin-1 is a better marker for epithelioid-type MPM than other mesothelioma markers because of its specificity and the simplicity of pathological assessment. Pleural intelectin-1 could be a useful diagnostic marker for MPM with applications in histopathological identification of MPM.

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Specific Expression of Human Intelectin-1 in Malignant Pleural Mesothelioma and Gastrointestinal Goblet Cells

et al. (2012) Specific Expression of Human Intelectin-1 in Malignant Pleural Mesothelioma and Gastrointestinal Goblet Cells. PLoS ONE 7(7): e39889. doi:10.1371/journal.pone.0039889 Specific Expression of Human Intelectin-1 in Malignant Pleural Mesothelioma and Gastrointestinal Goblet Cells Kota Washimi 0 Tomoyuki Yokose 0 Makiko Yamashita 0 Taihei Kageyama 0 Katsuo Suzuki 0 Mitsuyo Yoshihara 0 Yohei Miyagi 0 Hiroyuki Hayashi 0 Shoutaro Tsuji 0 Anthony W.I. Lo, The Chinese University of Hong Kong, Hong Kong 0 1 Department of Pathology, Kanagawa Cancer Center , Yokohama, Japan, 2 Molecular Diagnostic Project , Kanagawa Cancer Center Research Institute , Yokohama , Japan , 3 Division of Molecular Pathology and Genetics, Kanagawa Cancer Center Research Institute , Yokohama , Japan , 4 Department of Pathology, Yokohama Municipal Citizen's Hospital , Yokohama , Japan Malignant pleural mesothelioma (MPM) is a fatal tumor. It is often hard to discriminate MPM from metastatic tumors of other types because currently, there are no reliable immunopathological markers for MPM. MPM is differentially diagnosed by some immunohistochemical tests on pathology specimens. In the present study, we investigated the expression of intelectin-1, a new mesothelioma marker, in normal tissues in the whole body and in many cancers, including MPM, by immunohistochemical analysis. We found that in normal tissues, human intelectin-1 was mainly secreted from gastrointestinal goblet cells along with mucus into the intestinal lumen, and it was also expressed, to a lesser extent, in mesothelial cells and urinary epithelial cells. Eighty-eight percent of epithelioid-type MPMs expressed intelectin-1, whereas sarcomatoid-type MPMs, biphasic MPMs, and poorly differentiated MPMs were rarely positive for intelectin-1. Intelectin-1 was not expressed in other cancers, except in mucus-producing adenocarcinoma. These results suggest that intelectin-1 is a better marker for epithelioid-type MPM than other mesothelioma markers because of its specificity and the simplicity of pathological assessment. Pleural intelectin-1 could be a useful diagnostic marker for MPM with applications in histopathological identification of MPM. - Funding: This research was supported in part by the following grants: Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research (JSPS KAKENHI) (22590544), Immuno-Biological Laboratories Co., Ltd., and Takeda Science Foundation (to ST); the Grant-in-Aid for Collaboration between Hospital and Research Institute, Kanagawa Cancer Center (to KW). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have read the journals policy and have the following conflicts: Dr. Tsuji received research grants from Immuno-Biological Laboratories Co., Ltd. This does not alter the authors adherence to all the PLoS ONE policies on sharing data and materials. Malignant pleural mesothelioma (MPM) is a fatal tumor. The median survival of patients with MPM after chemotherapy or radical surgery is only 912 months [1]. Since MPM is correlated with prior exposure to asbestos [2], the number of people with MPM is increasing relative to the amount of asbestos used in the world [3,4]. It is often difficult to diagnose MPM and to distinguish it from metastatic carcinomas because a sensitive and reliable diagnostic marker for MPM has not been found yet. The differential diagnosis of MPM depends on some immunohistochemical tests of surgical pathology specimens. Calretinin, cytokeratin 5/6 (CK5/6), mesothelin, Wilms tumor gene product 1 (WT-1), and podoplanin, often referred to as D2-40, have been reported as immunohistochemical markers for epithelioid-type MPM [57]. Recently, we reported that a large amount of intelectin-1 is secreted into the malignant pleural fluid from epithelioid-type MPMs [8]. The intelectin gene was shown to be specifically expressed in cells of the small intestine [9]. Intelectin binds to galactofuranosyl residues and pathogens [10,11], and infection or inflammation causes an increase in the expression of intelectin mRNA in the intestine [12,13] or bronchus [14]. Human intelectin-1 is expressed in intestinal goblet cells, besides in MPMs, and is present at about 200 ng/mL in serum [8]. Intelectin-1 was also shown to be expressed in human endothelial cells [15] and adipocytes of human abdominal adipose tissue [16]. However, intelectin-1 expression in normal or cancerous tissues in humans has not been investigated yet with human intelectin-1-specific antibodies. In the present study, we analyzed intelectin-1 expression in human tissues lacking evident pathological lesions, and in some cancerous tissues, by immunohistochemical analysis using a monoclonal antibody against human intelectin-1. Intelectin-1 was expressed in gastrointestinal goblet cells, kidney collecting tubule cells, some bladder umbrella cells, (...truncated)


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Kota Washimi, Tomoyuki Yokose, Makiko Yamashita, Taihei Kageyama, Katsuo Suzuki, Mitsuyo Yoshihara, Yohei Miyagi, Hiroyuki Hayashi, Shoutaro Tsuji. Specific Expression of Human Intelectin-1 in Malignant Pleural Mesothelioma and Gastrointestinal Goblet Cells, PLOS ONE, 2012, 7, DOI: 10.1371/journal.pone.0039889