Department of Pathology, Stanford University School of Medicine, Stanford, CA, US.
Department of Medicine, Division of Hematology, Cancer Institute, Stanford, CA, US.
Am J Clin Pathol. 2024 Sep 3;162(3):269-281. doi: 10.1093/ajcp/aqae034.
Measurable residual disease flow cytometry (MRD-FC) and molecular studies are the most sensitive methods for detecting residual malignant populations after therapy for TP53-mutated acute myeloid leukemia and myelodysplastic neoplasms (TP53+ AML/MDS). However, their sensitivity is limited in suboptimal aspirates or when the immunophenotype of the neoplastic blasts overlaps with erythroids or normal maturing myeloid cells. In this study, we set out to determine if p53 immunohistochemistry (IHC) correlates with MRD-FC and next-generation sequencing (NGS) in the posttherapy setting and to determine the utility of p53 IHC to detect residual disease in the setting of negative or equivocal MRD-FC.
We retrospectively identified 28 pre- and posttherapy bone marrow biopsy specimens from 9 patients with TP53+ AML/MDS and a p53 overexpressor phenotype by IHC (strong 3+ staining at initial diagnosis). Next-generation sequencing and/or MRD-FC results were collected for each specimen.
Using a threshold of more than ten 2-3+ cells in any one 400× field, p53 IHC detected residual disease with a sensitivity of 94% and a specificity of 89%. The threshold used in this study showed a high degree of concordance among 6 blinded pathologists (Fleiss κ = 0.97).
Our study suggests that p53 IHC can be used as a rapid tool (within 24 hours) to aid in the detection of residual disease that may complement MRD-FC or NGS in cases in which the flow cytometry immunophenotype is equivocal and/or the bone marrow aspirate is suboptimal.
在治疗 TP53 突变急性髓系白血病和骨髓增生异常综合征（TP53+ AML/MDS）后，通过流式细胞术（MRD-FC）和分子研究等方法检测残留的恶性细胞，是最敏感的方法。然而，当抽吸物质量不佳或肿瘤细胞的免疫表型与红细胞或正常成熟髓系细胞重叠时，这些方法的灵敏度会受到限制。在这项研究中，我们旨在确定在治疗后，p53 免疫组织化学（IHC）与 MRD-FC 和下一代测序（NGS）是否相关，并确定在 MRD-FC 呈阴性或不确定时，p53 IHC 检测残留疾病的效用。
我们回顾性地鉴定了 9 名 TP53+ AML/MDS 患者的 28 份治疗前后骨髓活检标本，这些患者在初始诊断时通过 IHC（强 3+染色）表现出 p53 过表达表型。为每个标本收集了 NGS 和/或 MRD-FC 结果。
使用在任意一个 400×视野中超过十个 2-3+细胞的阈值，p53 IHC 检测到残留疾病的灵敏度为 94%，特异性为 89%。本研究中使用的阈值在 6 名盲法病理学家中显示出高度一致性（Fleiss κ=0.97）。
我们的研究表明，p53 IHC 可以作为一种快速工具（在 24 小时内），辅助检测残留疾病，在流式细胞术免疫表型不确定和/或骨髓抽吸物质量不佳的情况下，可补充 MRD-FC 或 NGS 的结果。
