Department of Pathology, Graduate School of Biomedical and Health Sciences.
Department of Surgical Oncology, Research Center for Radiation Casualty Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
Am J Surg Pathol. 2024 Feb 1;48(2):140-149. doi: 10.1097/PAS.0000000000002147. Epub 2023 Oct 30.
Epithelioid mesothelioma with a solid histologic pattern (solid epithelioid mesothelioma) is difficult to distinguish from a poorly differentiated squamous cell lung carcinoma and/or solid lung adenocarcinoma. Thus, immunohistochemical markers are essential for diagnosis; however, the sensitivity and specificity of pre-existing mesothelial markers are suboptimal, particularly for differentiation from squamous cell carcinoma. Using a cancer-dependency map, we analyzed gene expression data of pleural mesothelioma and non-small cell lung cancer cell lines (squamous cell carcinoma and adenocarcinoma) and identified secreted protein acidic and cysteine-rich (SPARC) as a promising candidate for the differential diagnosis of epithelioid mesothelioma from lung squamous cell carcinoma and/or lung adenocarcinoma. SPARC expression in mesothelioma and lung cancer cell lines was validated using reverse-transcription polymerase chain reaction, western blotting, and immunohistochemistry. Immunohistochemical staining was performed using anti-SPARC antibodies against solid epithelioid mesothelioma, solid lung adenocarcinoma, and poorly differentiated lung squamous cell carcinoma. SPARC positivity was seen in 42/45 (93.3%) of solid epithelioid mesothelioma, 2/40 (5%) solid lung adenocarcinoma, and 2/45 (4.5%) of lung squamous cell carcinomas. The sensitivity, specificity, and diagnostic accuracy for differentiating solid epithelioid mesothelioma from lung cancer (solid lung adenocarcinoma and poorly differentiated lung squamous cell carcinoma) were 93.3, 95.2, and 94.6%, respectively. In conclusion, SPARC is a novel mesothelial marker that can be used to differentiate epithelioid mesothelioma from squamous cell carcinoma and lung adenocarcinoma.
上皮样间皮瘤具有实性组织学模式（实性上皮样间皮瘤），难以与低分化鳞状细胞肺癌和/或实性肺腺癌区分。因此，免疫组织化学标志物对于诊断至关重要；然而，现有的间皮标志物的敏感性和特异性并不理想，特别是用于与鳞状细胞癌的区分。使用癌症依赖性图谱，我们分析了胸膜间皮瘤和非小细胞肺癌细胞系（鳞状细胞癌和腺癌）的基因表达数据，并确定富含天冬氨酸和半胱氨酸的分泌蛋白（SPARC）是鉴别上皮样间皮瘤与肺鳞状细胞癌和/或肺腺癌的有前途的候选物。使用逆转录聚合酶链反应、蛋白质印迹和免疫组织化学验证了间皮瘤和肺癌细胞系中 SPARC 的表达。使用针对实性上皮样间皮瘤、实性肺腺癌和低分化肺鳞状细胞癌的抗 SPARC 抗体进行免疫组织化学染色。在 45 例实性上皮样间皮瘤中的 42 例（93.3%）、40 例实性肺腺癌中的 2 例（5%）和 45 例肺鳞状细胞癌中的 2 例（4.5%）中观察到 SPARC 阳性。区分实性上皮样间皮瘤与肺癌（实性肺腺癌和低分化肺鳞状细胞癌）的敏感性、特异性和诊断准确性分别为 93.3%、95.2%和 94.6%。总之，SPARC 是一种新型的间皮标志物，可用于区分上皮样间皮瘤与鳞状细胞癌和肺腺癌。
