BAP1 丢失和 p16 (CDKN2A) 缺失分析对积液细胞学中间皮瘤的明确诊断的贡献。
Contribution of BAP1 loss and p16 (CDKN2A) deletion analysis to the definitive diagnosis of mesothelioma in effusion cytology.
发表日期:2023 Oct
作者:
G Aydogdu, S Özekinci
来源:
Protein & Cell
摘要:
间皮瘤的细胞学诊断是一个有争议的问题,明确的诊断通常需要辅助检查。本研究的目的是探讨 BRCA1 相关蛋白 (1) (BAP1) 缺失和 p16 (CDKN2A) 纯合缺失 (HD) 对积液中间皮瘤早期诊断的贡献。2019-2022 年间,21 例胸膜和该研究包括我们机构诊断为非典型间皮增殖的腹膜液样本。从档案中检索接受 BAP1 免疫组织化学 (IHC) 的病例的玻片并重新检查。通过荧光原位杂交 (FISH) 方法在细胞学样品的细胞块中研究 p16 (CDKN2A) 的纯合缺失 (HD)。每例至少计数100个非典型间皮细胞,HD阈值>10%。病例平均年龄63.47岁(34-90岁),女性/男性比例为3/1。胸膜间皮瘤病例中,16 例为上皮样,2 例为双相性,1 例为肉瘤样。 2例被诊断为腹膜高分化乳头状间皮瘤(WDPM)。 16 例中有 11 例 (69%) 观察到 BAP1 丢失。 11 名 (58%) 的 FISH 患者中发现 p16 (CDKN2A) 的 HD 缺失。 HD阈值为10-20%6例,30-50%3例,90%以上2例。虽然在所有双相性和肉瘤样病例的 p16 (CDKN2A) 中观察到 HD 缺失 (n=3),但在腹膜 WDPM 中未观察到缺失 (n=2)。在接受 BAP1 IHC 和 p16 (CDKN2A) FISH 的 14 例胸膜间皮瘤中,有 12 例 (86%) 通过至少一种方法观察到阳性。由于技术原因,无法在两个细胞块中获得FISH信号,因此无法获得结果。间皮瘤流行地区的石棉暴露和/或细胞学检查中存在增殖的间皮细胞是诊断的重要线索。在有争议的情况下,BAP1 IHC 应该是辅助测试的第一步。尽管应用于细胞块的 FISH 方法具有细胞学特异性的局限性和困难,但在选定的病例中使用 FISH 研究 p16 (CDKN2A) 缺失将有助于诊断。
The cytological diagnosis of mesothelioma is a controversial issue, and definitive diagnosis often requires ancillary tests. The aim of this study was to investigate the contribution of BRCA1-associated protein (1) (BAP1) loss and p16 (CDKN2A) homozygous deletion (HD) on the early diagnosis of mesothelioma in effusion fluids.Between 2019-2022, 21 pleural and peritoneal fluid samples diagnosed with atypical mesothelial proliferation in our institution were included in the study. The slides of the cases that underwent BAP1 immunohistochemistry (IHC) were retrieved from the archive and re-examined. Homozygous deletion (HD) of p16 (CDKN2A) was investigated by the fluorescence in situ hybridization (FISH) method in cell blocks of cytology samples. At least 100 atypical mesothelial cells were counted in each case, and the HD threshold value was >10%.The mean age of the cases was 63.47 years (34-90 years), female/male ratio was 3/1. Of the pleural mesothelioma cases, 16 were epithelioid, 2 were biphasic, and 1 were sarcomatoid. Two cases were diagnosed with peritoneal well-differentiated papillary mesothelioma (WDPM). BAP1 loss was observed in 11 (69%) of 16 cases. HD deletion of p16 (CDKN2A) was seen in 11 (58%) patients with FISH. The HD threshold value was 10-20% in 6 of the cases, 30-50% in 3 cases, and above 90% in 2 cases. While HD deletion was observed in p16 (CDKN2A) in all biphasic and sarcomatoid cases (n=3), no deletion was observed in peritoneal WDPM (n=2). Positivity was observed with at least one method in 12 (86%) of 14 pleural mesotheliomas who underwent both BAP1 IHC and p16 (CDKN2A) FISH. Due to technical reasons, the FISH signal could not be obtained in two cell blocks, so no results could be obtained.Asbestos exposure in areas where mesothelioma is endemic and/or the presence of proliferating mesothelial cells in cytological examination are important clues for diagnosis. In controversial cases, BAP1 IHC should be the first step in an ancillary test. Although the FISH method applied to cell blocks has cytology-specific limitations and difficulties, investigating the p16 (CDKN2A) deletion with FISH in selected cases will contribute to the diagnosis.