Katsuragi Shin-Ya, Sakano Yuri, Ohta Isao, Kato Hisami, Ishikawa Rei, Watanabe Hirofumi, Miyazaki Ryosuke, Yoshimura Katsuhiro, Yamada Hidetaka, Sakai Yasuhiro, Inoue Yusuke, Takanashi Yusuke, Sekihara Keigo, Funai Kazuhito, Otsuki Yoshiro, Kawasaki Hideya, Shinmura Kazuya
Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan.
NanoSuit Research Laboratory, Division of Preeminent Bioimaging Research, Institute of Photonics Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan.
Diagnostics (Basel). 2025 May 21;15(10):1298. doi: 10.3390/diagnostics15101298.
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. 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%; < 0.0001) or LSCC (43.5%; = 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. 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.
鉴别胸部恶性肿瘤，如上皮样恶性胸膜间皮瘤（EMPM）和非小细胞肺癌（NSCLC），后者主要包括肺腺癌（LAC）和肺鳞状细胞癌（LSCC），在常规病理诊断中仍然是一项挑战。本研究旨在评估采用NanoSuit相关光电子显微镜（CLEM）方法的足突蛋白（PDPN）免疫组织化学结合扫描电子显微镜（SEM）是否可作为区分这些胸部恶性肿瘤的可靠工具。最初，通过免疫组织化学分析评估了11例EMPM、100例LAC和23例LSCC病例中的PDPN表达。PDPN阳性主要见于细胞膜，在EMPM中（100%）比在LAC（2%；<0.0001）或LSCC（43.5%；=0.0018）中更常见。随后，使用NanoSuit-CLEM方法对免疫组织化学切片上的PDPN阳性部位进行场发射扫描电子显微镜（FE-SEM）观察，发现了独特的超微结构特征。EMPM表现为密集排列的细长微绒毛，而LAC和LSCC中则没有这种结构。此外，对厚切片（20μm）的分析显示了EMPM特有的广泛微绒毛覆盖。这些发现表明，采用NanoSuit-CLEM方法的PDPN免疫组织化学和PDPN阳性部位的FE-SEM观察相结合的方法，构成了一种有效的诊断策略，可提高区分EMPM与NSCLC的准确性。
