Identification of Novel Diagnostic Markers for Malignant Pleural Mesothelioma Using a Reverse Translational Approach Based on a Rare Synchronous Tumor
Although the routine use of immunohistochemistry has improved the accuracy of histopathologic diagnosis in clinical practice, new methods for discovering novel diagnostic markers are still needed. We sought new diagnostic markers for malignant pleural mesothelioma (MPM) using a reverse translational...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-01-01
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| Series: | Diagnostics |
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| Online Access: | https://www.mdpi.com/2075-4418/12/2/316 |
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| author | Tomoaki Naka Yutaka Hatanaka Yukiko Tabata Akira Takasawa Hideo Akiyama Yasuhiro Hida Hiromi Okada Kanako C. Hatanaka Tomoko Mitsuhashi Kei Kushitani Vishwa Jeet Amatya Yukio Takeshima Kouki Inai Kichizo Kaga Yoshihiro Matsuno |
| author_facet | Tomoaki Naka Yutaka Hatanaka Yukiko Tabata Akira Takasawa Hideo Akiyama Yasuhiro Hida Hiromi Okada Kanako C. Hatanaka Tomoko Mitsuhashi Kei Kushitani Vishwa Jeet Amatya Yukio Takeshima Kouki Inai Kichizo Kaga Yoshihiro Matsuno |
| author_sort | Tomoaki Naka |
| collection | DOAJ |
| description | Although the routine use of immunohistochemistry has improved the accuracy of histopathologic diagnosis in clinical practice, new methods for discovering novel diagnostic markers are still needed. We sought new diagnostic markers for malignant pleural mesothelioma (MPM) using a reverse translational approach with limited archival tissues from a very rare case. Total RNA extracted from formalin-fixed paraffin-embedded (FFPE) tissues of a synchronous collision tumor consisting of MPM and pulmonary adenocarcinoma (PAC) was employed for gene expression profiling (GEP) analysis. Among the 54 genes selected by GEP analysis, we finally identified the following two candidate MPM marker genes: <i>PHGDH</i> and <i>TRIM29</i>. Immunohistochemical analysis of 48 MM and 20 PAC cases showed that both PHGDH and TRIM29 had sensitivity and specificity almost equivalent to those of calretinin (sensitivity 50% and 46% vs. 63%, and specificity 95% and 100% vs. 100%, respectively). Importantly, of the 23 epithelioid MMs, all 3 calretinin-negative cases were positive for TRIM29. These two markers may be diagnostically useful for immunohistochemical distinction between MPMs and PACs. This successful reverse translational approach based on FFPE samples from one very rare case encourages the further use of such samples for the development of novel diagnostic markers. |
| first_indexed | 2024-03-09T22:12:06Z |
| format | Article |
| id | doaj.art-3320f9c47ffa4aa19288f39257050aa8 |
| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-03-09T22:12:06Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Diagnostics |
| spelling | doaj.art-3320f9c47ffa4aa19288f39257050aa82023-11-23T19:30:03ZengMDPI AGDiagnostics2075-44182022-01-0112231610.3390/diagnostics12020316Identification of Novel Diagnostic Markers for Malignant Pleural Mesothelioma Using a Reverse Translational Approach Based on a Rare Synchronous TumorTomoaki Naka0Yutaka Hatanaka1Yukiko Tabata2Akira Takasawa3Hideo Akiyama4Yasuhiro Hida5Hiromi Okada6Kanako C. Hatanaka7Tomoko Mitsuhashi8Kei Kushitani9Vishwa Jeet Amatya10Yukio Takeshima11Kouki Inai12Kichizo Kaga13Yoshihiro Matsuno14Department of Surgical Pathology, Hokkaido University Hospital, Sapporo 060-8648, JapanDepartment of Surgical Pathology, Hokkaido University Hospital, Sapporo 060-8648, JapanDepartment of Surgical Pathology, Hokkaido University Hospital, Sapporo 060-8648, JapanDepartment of Surgical Pathology, Hokkaido University Hospital, Sapporo 060-8648, JapanResearch Division of Genome Companion Diagnostics, Hokkaido University Hospital, Sapporo 060-8648, JapanDepartment of Cardiovascular and Thoracic Surgery, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, JapanDepartment of Surgical Pathology, Hokkaido University Hospital, Sapporo 060-8648, JapanDepartment of Surgical Pathology, Hokkaido University Hospital, Sapporo 060-8648, JapanDepartment of Surgical Pathology, Hokkaido University Hospital, Sapporo 060-8648, JapanDepartment of Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, JapanDepartment of Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, JapanDepartment of Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, JapanDepartment of Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, JapanDepartment of Cardiovascular and Thoracic Surgery, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, JapanDepartment of Surgical Pathology, Hokkaido University Hospital, Sapporo 060-8648, JapanAlthough the routine use of immunohistochemistry has improved the accuracy of histopathologic diagnosis in clinical practice, new methods for discovering novel diagnostic markers are still needed. We sought new diagnostic markers for malignant pleural mesothelioma (MPM) using a reverse translational approach with limited archival tissues from a very rare case. Total RNA extracted from formalin-fixed paraffin-embedded (FFPE) tissues of a synchronous collision tumor consisting of MPM and pulmonary adenocarcinoma (PAC) was employed for gene expression profiling (GEP) analysis. Among the 54 genes selected by GEP analysis, we finally identified the following two candidate MPM marker genes: <i>PHGDH</i> and <i>TRIM29</i>. Immunohistochemical analysis of 48 MM and 20 PAC cases showed that both PHGDH and TRIM29 had sensitivity and specificity almost equivalent to those of calretinin (sensitivity 50% and 46% vs. 63%, and specificity 95% and 100% vs. 100%, respectively). Importantly, of the 23 epithelioid MMs, all 3 calretinin-negative cases were positive for TRIM29. These two markers may be diagnostically useful for immunohistochemical distinction between MPMs and PACs. This successful reverse translational approach based on FFPE samples from one very rare case encourages the further use of such samples for the development of novel diagnostic markers.https://www.mdpi.com/2075-4418/12/2/316malignant pleural mesotheliomagene expression profilingimmunohistochemistry |
| spellingShingle | Tomoaki Naka Yutaka Hatanaka Yukiko Tabata Akira Takasawa Hideo Akiyama Yasuhiro Hida Hiromi Okada Kanako C. Hatanaka Tomoko Mitsuhashi Kei Kushitani Vishwa Jeet Amatya Yukio Takeshima Kouki Inai Kichizo Kaga Yoshihiro Matsuno Identification of Novel Diagnostic Markers for Malignant Pleural Mesothelioma Using a Reverse Translational Approach Based on a Rare Synchronous Tumor Diagnostics malignant pleural mesothelioma gene expression profiling immunohistochemistry |
| title | Identification of Novel Diagnostic Markers for Malignant Pleural Mesothelioma Using a Reverse Translational Approach Based on a Rare Synchronous Tumor |
| title_full | Identification of Novel Diagnostic Markers for Malignant Pleural Mesothelioma Using a Reverse Translational Approach Based on a Rare Synchronous Tumor |
| title_fullStr | Identification of Novel Diagnostic Markers for Malignant Pleural Mesothelioma Using a Reverse Translational Approach Based on a Rare Synchronous Tumor |
| title_full_unstemmed | Identification of Novel Diagnostic Markers for Malignant Pleural Mesothelioma Using a Reverse Translational Approach Based on a Rare Synchronous Tumor |
| title_short | Identification of Novel Diagnostic Markers for Malignant Pleural Mesothelioma Using a Reverse Translational Approach Based on a Rare Synchronous Tumor |
| title_sort | identification of novel diagnostic markers for malignant pleural mesothelioma using a reverse translational approach based on a rare synchronous tumor |
| topic | malignant pleural mesothelioma gene expression profiling immunohistochemistry |
| url | https://www.mdpi.com/2075-4418/12/2/316 |
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