Department of Biochemistry and Genetics, Chiba University Graduate School of Medicine, Chiba, Japan.
Department of Pathology, Tokyo Women's Medical University, Yachiyo Medical Center, Yachiyo, Japan.
Diagn Cytopathol. 2021 May;49(5):622-632. doi: 10.1002/dc.24475. Epub 2020 May 22.
The specificity and sensitivity of HEG1 for malignant mesothelioma (MM) is high. The use of BAP1/MTAP immunohistochemistry (IHC) is recommended to separate benign and malignant mesothelial proliferations. We determined how ancillary techniques can be used for the cytological diagnosis of MM with effusion.
Cell blocks from effusions from cases with MM, reactive mesothelial cells (RMCs), and carcinomas were analyzed by IHC with HEG1, BAP1, and MTAP and with homozygous deletion (HD) of CDKN2A by fluorescence in situ hybridization. Staining scores were calculated for IHC by adding the number of categories for the staining intensity and the staining extension.
HEG1 was positive in all (41/41) MMs, but negative in carcinomas, except for ovarian carcinomas. Overall 76.9% (20/26) of RMCs and 28.6% (6/21) of ovarian carcinomas expressed HEG1. BAP1 loss was found in 71.1% of MMs, but none was found in RMCs. MTAP loss was found in 76.2% of MMs, but none was found in RMCs. 73.9% of MMs harbored HD of CDKN2A. There was concordance between loss of MTAP and HD of CDKN2A in 95% of MMs.
HEG1 is a good marker for mesothelial differentiation in effusion cytology. HD of CDKN2A is frequently observed in cell blocks from effusions of MMs, and MTAP IHC may act as a surrogate for HD of CDKN2A. Cell block analysis is recommended for effusions of unknown origins with the following methods: IHC with HEG1 and claudin 4 to validate the mesothelial origin, followed by BAP1 and MTAP IHC to confirm malignancy.
HEG1 对恶性间皮瘤（MM）具有很高的特异性和敏感性。建议使用 BAP1/MTAP 免疫组化（IHC）来区分良性和恶性间皮细胞增生。我们确定了辅助技术如何用于胸腔积液中 MM 的细胞学诊断。
对来自 MM、反应性间皮细胞（RMC）和癌病例的胸腔积液细胞块进行 IHC 分析，使用 HEG1、BAP1 和 MTAP 以及荧光原位杂交进行 CDKN2A 纯合缺失（HD）。通过将染色强度和染色扩展的类别数量相加来计算 IHC 的染色评分。
HEG1 在所有（41/41）MM 中均为阳性，但在除卵巢癌外的所有癌中均为阴性。总体而言，76.9%（20/26）的 RMC 和 28.6%（6/21）的卵巢癌表达 HEG1。71.1%的 MM 中发现 BAP1 缺失，但在 RMC 中未发现。76.2%的 MM 中发现 MTAP 缺失，但在 RMC 中未发现。73.9%的 MM 存在 CDKN2A 的 HD。在 95%的 MM 中，MTAP 缺失与 CDKN2A 的 HD 之间存在一致性。
HEG1 是胸腔积液细胞学中间皮分化的良好标志物。HD of CDKN2A 经常在 MM 胸腔积液细胞块中观察到，MTAP IHC 可作为 CDKN2A HD 的替代物。建议对来源不明的胸腔积液进行细胞块分析，方法如下：使用 HEG1 和 Claudin 4 进行 IHC，以验证间皮起源，然后进行 BAP1 和 MTAP IHC，以确认恶性肿瘤。
