Fernandez-Pol Sebastian, Ma Lisa, Ohgami Robert S, Arber Daniel A
Department of Pathology, Stanford University, Stanford, CA, USA.
Mod Pathol. 2017 Mar;30(3):382-392. doi: 10.1038/modpathol.2016.206. Epub 2016 Dec 9.
In this study, we evaluate the expression of p53 in core biopsies with acute myeloid leukemia and correlate the level of expression with acute myeloid leukemia subtype, TP53 mutation status, karyotype, and survival. Of the 143 cases evaluated, 71 fulfilled the WHO 2016 criteria for acute myeloid leukemia with myelodysplasia-related changes, 40 were acute myeloid leukemia-not otherwise specified, 25 were acute myeloid leukemia with recurrent genetic abnormalities, and 7 were therapy-related acute myeloid leukemia. By immunohistochemistry, 17% showed p53 expression in >5% of the cells. Of the 24 cases with >5% p53-positive cells, 17 were acute myeloid leukemia with myelodysplasia-related changes, 5 were acute myeloid leukemia-not otherwise specified, 1 was acute myeloid leukemia with recurrent genetic abormalities, and 1 was therapy-related acute myeloid leukemia. In cases for which data was available, expression of >5% p53-positive cells was significantly associated with genotype (n=67) and/or karyotype (n=130). Among the 115 cases for which clinical follow up was available, the overall survival of cases with p53 expression >15% (Median=102 days) was significantly shorter compared with cases with p53 expression ≤15% (Median=435 days). Within the acute myeloid leukemia with myelodysplasia-related changes group, this association remained significant, with cases with ≤15% p53-positive cells having a median overall survival of 405 days versus 102 days for cases with >15% p53-positive cells. Among acute myeloid leukemia with myelodysplasia-related changes cases with a complex karyotype, the finding of >15% p53-positive cells was significantly associated with worse overall survival. The poor prognosis associated with more than 15% p53-positive cells was independent of age and karyotype. In acute myeloid leukemia with myelodysplasia-related changes, p53 expression may be useful to infer TP53 mutation status, complex karyotype, and/or poor prognosis in situations where other modalities are not readily available.
在本研究中,我们评估了急性髓系白血病患者核心活检组织中p53的表达情况,并将其表达水平与急性髓系白血病亚型、TP53突变状态、核型及生存率进行关联分析。在评估的143例病例中,71例符合世界卫生组织2016年关于伴有骨髓增生异常相关改变的急性髓系白血病的标准,40例为非特指型急性髓系白血病,25例为伴有复发性基因异常的急性髓系白血病,7例为治疗相关的急性髓系白血病。通过免疫组化检测,17%的病例显示超过5%的细胞有p53表达。在24例p53阳性细胞>5%的病例中,17例为伴有骨髓增生异常相关改变的急性髓系白血病,5例为非特指型急性髓系白血病,1例为伴有复发性基因异常的急性髓系白血病,1例为治疗相关的急性髓系白血病。在有可用数据的病例中,p53阳性细胞>5%的表达与基因型(n = 67)和/或核型(n = 130)显著相关。在有临床随访数据的115例病例中,p53表达>15%的病例(中位生存期=102天)的总生存期显著短于p53表达≤15%的病例(中位生存期=435天)。在伴有骨髓增生异常相关改变的急性髓系白血病组中,这种关联仍然显著,p53阳性细胞≤15%的病例中位总生存期为405天,而p53阳性细胞>15%的病例为102天。在伴有复杂核型的伴有骨髓增生异常相关改变的急性髓系白血病病例中,p53阳性细胞>15%与较差的总生存期显著相关。p53阳性细胞超过15%所带来的不良预后与年龄和核型无关。在伴有骨髓增生异常相关改变的急性髓系白血病中,在其他检测手段难以实施的情况下,p53表达可能有助于推断TP53突变状态、复杂核型和/或不良预后。