The Lauren V. Ackerman Laboratory of Surgical Pathology, Barnes-Jewish and St. Louis Children's Hospitals, Washington University Medical Center, St. Louis, MO, USA.
Department of Pathology, Yale School of Medicine, New Haven, CT, USA.
Mod Pathol. 2021 Jun;34(6):1104-1115. doi: 10.1038/s41379-021-00735-8. Epub 2021 Feb 26.
Pleuropulmonary blastoma (PPB) is a primary embryonal malignancy of childhood that is characterized by distinct morphologic types: type Ir (regressed), type I (cystic), type II (cystic and solid), and type III (solid). Prognosis varies by PPB type. Most cases are associated with a germline pathogenic mutation in DICER1; however, there is limited data on the factor(s) at a cellular level that drive progression from type I to type III. In this study, we evaluated the expression of p53 and its prognostic implications. A total of 143 PPB cases were included in the study with the following distribution in PPB types: Ir (14%), I (23%), II (32%), and III (31%). P53 expression by immunohistochemistry (IHC) was recorded as four groups: 0%, 1-25%, 26-75%, and 76-100%. All type I PPBs showed 0-25% p53 expression compared to the higher p53 expression (>25%) in type III PPB (p < 0.0001), to support the argument that p53 has a role in tumor progression. In addition, type Ir with the architectural hallmarks of type I PPB, but lacking the primitive cell population, has negligible p53 expression. High p53 expression (staining observed in >25% of the tumor cells) was significantly associated with age over 1 year (p = 0.0033), neoadjuvant therapy (p = 0.0009), positive resection margin (p = 0.0008) and anaplasia (p < 0.0001). P53 expression was significantly associated with recurrence-free survival (p < 0.0001) and overall survival (p = 0.0350), with higher p53 expression associated with worse prognosis. Comparisons of concordance statistics showed no significant difference in prognostication when using morphologic types compared to p53 expression groups (p = 0.647). TP53 sequence was performed in 16 cases; the most common variant identified was a missense variant (12 cases), and in one case a frameshift truncating variant was noted. Based on these findings, we recommend performing p53 IHC in all newly diagnosed cases of types II and III PPB to further aid in risk stratification.
肺胚细胞瘤 (PPB) 是一种儿童期的原发性胚胎恶性肿瘤，其特征为具有不同的形态类型：I 型 (消退型)、I 型 (囊性)、II 型 (囊性和实性) 和 III 型 (实性)。PPB 类型不同，预后也不同。大多数病例与 DICER1 种系致病性突变有关；然而，在细胞水平上，驱动从 I 型向 III 型进展的因素有限。在这项研究中，我们评估了 p53 的表达及其预后意义。共有 143 例 PPB 病例纳入研究，其 PPB 类型分布如下：I 型 (14%)、I 型 (23%)、II 型 (32%) 和 III 型 (31%)。通过免疫组织化学 (IHC) 记录 p53 的表达，分为四组：0%、1-25%、26-75%和 76-100%。所有 I 型 PPB 的 p53 表达为 0-25%，而 III 型 PPB 的 p53 表达较高 (>25%) (p<0.0001)，支持 p53 在肿瘤进展中起作用的观点。此外，具有 I 型 PPB 结构特征但缺乏原始细胞群的 Ir 型，p53 表达可忽略不计。高 p53 表达 (在>25%的肿瘤细胞中观察到染色) 与年龄>1 岁 (p=0.0033)、新辅助治疗 (p=0.0009)、阳性切缘 (p=0.0008) 和间变 (p<0.0001) 显著相关。p53 表达与无复发生存率 (p<0.0001) 和总生存率 (p=0.0350) 显著相关，p53 表达越高，预后越差。比较形态类型与 p53 表达组的预后预测一致性统计，发现差异无统计学意义 (p=0.647)。在 16 例中进行了 TP53 序列分析，最常见的变异是错义变异 (12 例)，在 1 例中发现了移码截断变异。基于这些发现，我们建议对所有新诊断的 II 型和 III 型 PPB 病例进行 p53 IHC，以进一步辅助风险分层。
