Liquid-based cytology (LBC) is now a widely used method for cytologic screening and cancer diagnosis. Since the cells are fixed with alcohol-based fixatives, and the specimens are stored in a liquid condition, LBC specimens are suitable for genetic analyses. Here, we established a small cancer gene panel, including 60 genes and 17 microsatellite markers for next-generation sequencing, and applied to residual LBC specimens obtained by endometrial cancer screening to compare with corresponding formalin-fixed paraffin-embedded (FFPE) tissues. A total of 49 FFPE and LBC specimens (n = 24) were analyzed, revealing characteristic mutations for endometrial cancer, including PTEN, CTNNB1, PIK3CA, and PIK3R1 mutations. Eight cases had higher scores for both tumor mutation burden (TMB) and microsatellite instability (MSI), which agree with defective mismatch repair (MMR) protein expression. Paired endometrial LBC, and biopsied and/or resected FFPE tissues from 7 cases, presented almost identical mutations, TMB, and MSI profiles in all cases. These findings demonstrate that our ad hoc cancer gene panel enabled the detection of therapeutically actionable gene mutations in endometrial LBC and FFPE specimens. Endometrial cancer LBC specimens offer an alternative and affordable source of molecular testing materials.

中文翻译：

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子宫内膜筛查液基细胞学标本的下一代测序分析：与组织标本的比较研究。

基于液体的细胞学（LBC）现在是用于细胞学筛查和癌症诊断的一种广泛使用的方法。由于细胞用酒精基固定剂固定，并且标本以液态保存，因此LBC标本适合进行遗传分析。在这里，我们建立了一个小型癌症基因组，包括用于下一代测序的60个基因和17个微卫星标记，并将其应用于通过子宫内膜癌筛查获得的残留LBC标本，以与相应的福尔马林固定石蜡包埋（FFPE）组织进行比较。共分析了49个FFPE和LBC标本（n = 24），揭示了子宫内膜癌的特征性突变，包括PTEN，CTNNB1，PIK3CA和PIK3R1突变。8例肿瘤突变负担（TMB）和微卫星不稳定性（MSI）得分均较高，与缺陷错配修复（MMR）蛋白表达相符。配对的子宫内膜LBC以及7例活检和/或切除的FFPE组织在所有病例中均表现出几乎相同的突变，TMB和MSI特征。这些发现表明，我们的特设癌症基因组能够检测子宫内膜LBC和FFPE标本中具有治疗作用的基因突变。子宫内膜癌LBC标本提供了一种替代且负担得起的分子检测材料。