Diagnostic Utility of Podoplanin Immunohistochemistry Combined with the NanoSuit-Correlative Light and Electron Microscopy Method for Thoracic Malignant Tumors

<b>Background/Objectives:</b> Differentiating thoracic malignant tumors, such as epithelioid malignant pleural mesothelioma (EMPM) and non-small-cell lung carcinoma (NSCLC), primarily comprising lung adenocarcinoma (LAC) and lung squamous cell carcinoma (LSCC), remains a challenge in rou...

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Main Authors: Shin-ya Katsuragi, Yuri Sakano, Isao Ohta, Hisami Kato, Rei Ishikawa, Hirofumi Watanabe, Ryosuke Miyazaki, Katsuhiro Yoshimura, Hidetaka Yamada, Yasuhiro Sakai, Yusuke Inoue, Yusuke Takanashi, Keigo Sekihara, Kazuhito Funai, Yoshiro Otsuki, Hideya Kawasaki, Kazuya Shinmura
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Diagnostics
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Online Access:https://www.mdpi.com/2075-4418/15/10/1298
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author Shin-ya Katsuragi
Yuri Sakano
Isao Ohta
Hisami Kato
Rei Ishikawa
Hirofumi Watanabe
Ryosuke Miyazaki
Katsuhiro Yoshimura
Hidetaka Yamada
Yasuhiro Sakai
Yusuke Inoue
Yusuke Takanashi
Keigo Sekihara
Kazuhito Funai
Yoshiro Otsuki
Hideya Kawasaki
Kazuya Shinmura
author_facet Shin-ya Katsuragi
Yuri Sakano
Isao Ohta
Hisami Kato
Rei Ishikawa
Hirofumi Watanabe
Ryosuke Miyazaki
Katsuhiro Yoshimura
Hidetaka Yamada
Yasuhiro Sakai
Yusuke Inoue
Yusuke Takanashi
Keigo Sekihara
Kazuhito Funai
Yoshiro Otsuki
Hideya Kawasaki
Kazuya Shinmura
author_sort Shin-ya Katsuragi
collection DOAJ
description <b>Background/Objectives:</b> Differentiating thoracic malignant tumors, such as epithelioid malignant pleural mesothelioma (EMPM) and non-small-cell lung carcinoma (NSCLC), primarily comprising lung adenocarcinoma (LAC) and lung squamous cell carcinoma (LSCC), remains a challenge in routine pathological diagnosis. This study aimed to evaluate whether podoplanin (PDPN) immunohistochemistry combined with scanning electron microscopy (SEM) using the NanoSuit-correlative light and electron microscopy (CLEM) methods could serve as a reliable tool for distinguishing these thoracic malignancies. <b>Methods/Results:</b> Initially, PDPN expression was assessed by immunohistochemical analysis in 11 EMPM, 100 LAC, and 23 LSCC cases. PDPN positivity was predominantly observed in the cell membrane and was significantly more frequent in EMPM (100%) than in LAC (2%; <i>p</i> < 0.0001) or LSCC (43.5%; <i>p</i> = 0.0018). Subsequently, field emission–SEM (FE-SEM) observations of PDPN-positive sites on immunohistochemical slides, conducted using the NanoSuit-CLEM method, revealed distinctive ultrastructural features. EMPM exhibited densely packed, elongated microvilli, whereas such structures were absent in LAC and LSCC. Furthermore, analysis of thick-cut sections (20 μm) demonstrated extensive microvilli coverage characteristic of EMPM. <b>Conclusions:</b> These findings suggest that the combined approach of PDPN immunohistochemistry and FE-SEM observation of PDPN-positive sites, using the NanoSuit-CLEM method, constitutes an effective diagnostic strategy for enhancing the accuracy of distinguishing EMPM from NSCLCs.
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spelling doaj-art-84b3cdeba790499b8043b8d7791748732025-08-20T02:33:59ZengMDPI AGDiagnostics2075-44182025-05-011510129810.3390/diagnostics15101298Diagnostic Utility of Podoplanin Immunohistochemistry Combined with the NanoSuit-Correlative Light and Electron Microscopy Method for Thoracic Malignant TumorsShin-ya Katsuragi0Yuri Sakano1Isao Ohta2Hisami Kato3Rei Ishikawa4Hirofumi Watanabe5Ryosuke Miyazaki6Katsuhiro Yoshimura7Hidetaka Yamada8Yasuhiro Sakai9Yusuke Inoue10Yusuke Takanashi11Keigo Sekihara12Kazuhito Funai13Yoshiro Otsuki14Hideya Kawasaki15Kazuya Shinmura16Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanNanoSuit Research Laboratory, Division of Preeminent Bioimaging Research, Institute of Photonics Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanAdvanced Research Facilities and Services, Division of Preeminent Research Supports, Institute of Photonics Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanDepartment of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanDepartment of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanDepartment of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanDepartment of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanDepartment of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanDepartment of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanDepartment of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanSecond Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanDepartment of Surgery 1, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanDepartment of Surgery 1, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanDepartment of Surgery 1, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanDepartment of Pathology, Seirei Hamamatsu General Hospital, Hamamatsu 430-8558, JapanNanoSuit Research Laboratory, Division of Preeminent Bioimaging Research, Institute of Photonics Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanDepartment of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan<b>Background/Objectives:</b> Differentiating thoracic malignant tumors, such as epithelioid malignant pleural mesothelioma (EMPM) and non-small-cell lung carcinoma (NSCLC), primarily comprising lung adenocarcinoma (LAC) and lung squamous cell carcinoma (LSCC), remains a challenge in routine pathological diagnosis. This study aimed to evaluate whether podoplanin (PDPN) immunohistochemistry combined with scanning electron microscopy (SEM) using the NanoSuit-correlative light and electron microscopy (CLEM) methods could serve as a reliable tool for distinguishing these thoracic malignancies. <b>Methods/Results:</b> Initially, PDPN expression was assessed by immunohistochemical analysis in 11 EMPM, 100 LAC, and 23 LSCC cases. PDPN positivity was predominantly observed in the cell membrane and was significantly more frequent in EMPM (100%) than in LAC (2%; <i>p</i> < 0.0001) or LSCC (43.5%; <i>p</i> = 0.0018). Subsequently, field emission–SEM (FE-SEM) observations of PDPN-positive sites on immunohistochemical slides, conducted using the NanoSuit-CLEM method, revealed distinctive ultrastructural features. EMPM exhibited densely packed, elongated microvilli, whereas such structures were absent in LAC and LSCC. Furthermore, analysis of thick-cut sections (20 μm) demonstrated extensive microvilli coverage characteristic of EMPM. <b>Conclusions:</b> These findings suggest that the combined approach of PDPN immunohistochemistry and FE-SEM observation of PDPN-positive sites, using the NanoSuit-CLEM method, constitutes an effective diagnostic strategy for enhancing the accuracy of distinguishing EMPM from NSCLCs.https://www.mdpi.com/2075-4418/15/10/1298epithelioid malignant pleural mesothelioma (EMPM)lung adenocarcinoma (LAC)lung squamous cell carcinoma (LSCC)microvilliNanoSuit-correlative light and electron microscopy (CLEM) methodnon-small-cell lung carcinoma (NSCLC)
spellingShingle Shin-ya Katsuragi
Yuri Sakano
Isao Ohta
Hisami Kato
Rei Ishikawa
Hirofumi Watanabe
Ryosuke Miyazaki
Katsuhiro Yoshimura
Hidetaka Yamada
Yasuhiro Sakai
Yusuke Inoue
Yusuke Takanashi
Keigo Sekihara
Kazuhito Funai
Yoshiro Otsuki
Hideya Kawasaki
Kazuya Shinmura
Diagnostic Utility of Podoplanin Immunohistochemistry Combined with the NanoSuit-Correlative Light and Electron Microscopy Method for Thoracic Malignant Tumors
Diagnostics
epithelioid malignant pleural mesothelioma (EMPM)
lung adenocarcinoma (LAC)
lung squamous cell carcinoma (LSCC)
microvilli
NanoSuit-correlative light and electron microscopy (CLEM) method
non-small-cell lung carcinoma (NSCLC)
title Diagnostic Utility of Podoplanin Immunohistochemistry Combined with the NanoSuit-Correlative Light and Electron Microscopy Method for Thoracic Malignant Tumors
title_full Diagnostic Utility of Podoplanin Immunohistochemistry Combined with the NanoSuit-Correlative Light and Electron Microscopy Method for Thoracic Malignant Tumors
title_fullStr Diagnostic Utility of Podoplanin Immunohistochemistry Combined with the NanoSuit-Correlative Light and Electron Microscopy Method for Thoracic Malignant Tumors
title_full_unstemmed Diagnostic Utility of Podoplanin Immunohistochemistry Combined with the NanoSuit-Correlative Light and Electron Microscopy Method for Thoracic Malignant Tumors
title_short Diagnostic Utility of Podoplanin Immunohistochemistry Combined with the NanoSuit-Correlative Light and Electron Microscopy Method for Thoracic Malignant Tumors
title_sort diagnostic utility of podoplanin immunohistochemistry combined with the nanosuit correlative light and electron microscopy method for thoracic malignant tumors
topic epithelioid malignant pleural mesothelioma (EMPM)
lung adenocarcinoma (LAC)
lung squamous cell carcinoma (LSCC)
microvilli
NanoSuit-correlative light and electron microscopy (CLEM) method
non-small-cell lung carcinoma (NSCLC)
url https://www.mdpi.com/2075-4418/15/10/1298
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