Int J Gynecol Pathol. 2021 Mar 1;40(2):116-123. doi: 10.1097/PGP.0000000000000674.
TP53 status is the most important prognostic biomarker in endometrial carcinoma. We asked the question whether p53 mutated endometrial endometrioid carcinomas grade 3 (EEC3) or endometrial serous carcinomas (ESC), the latter ubiquitously harboring TP53 mutation, have different outcomes. TP53 mutation status was assessed by surrogate p53 immunohistochemistry on 326 EEC3 and ESC from 2 major cancer centers in Canada. Mutant-type p53 expression, including overexpression, complete absence, or cytoplasmic expression, was distinguished from the wild-type pattern. Statistical associations with clinico-pathological parameter, other key biomarkers, and survival analyses were performed. P53 mutant-type immunohistochemistry was observed in all 126 ESC and in 47/200 (23.5%) EEC3. ESC and p53 mutated EEC3 had an unfavorable outcome compared with p53 wild-type EEC3 (hazard ratio=2.37, 95% confidence interval=1.48-3.80, P=0.003, hazard ratio=2.19, 95% confidence interval=1.16-4.12, P=0.016, respectively) in multivariable analyses adjusted for age, stage, center, and presence of lymph-vascular invasion. There was no significant difference in survival between ESC and p53 mutated EEC3 in multivariable analysis. Furthermore, p53 mutated EEC3 and ESC almost completely overlapped in univariate survival analysis when mismatch repair (MMR)-deficient cases were excluded, which suggests that EEC3 harboring combined MMR deficiency and TP53 mutations behave more according to the MMR status. Significant differences between p53 mutated MMR-proficient EEC3 and ESC in PTEN and p16 expression status remained. p53 mutated, MMR-proficient EEC3 and ESC have overlapping survival significantly different from p53 wild-type EEC3, which justifies a similar treatment with current non-targeted standard therapy. Although this is so, separate classification should continue due to biological differences that will become important for future targeted therapy.
TP53 状态是子宫内膜癌最重要的预后生物标志物。我们提出了这样一个问题，即 p53 突变的子宫内膜内膜样癌 3 级（EEC3）或子宫内膜浆液性癌（ESC），后者普遍存在 TP53 突变，是否具有不同的结局。我们在加拿大的 2 个主要癌症中心的 326 例 EEC3 和 ESC 中，通过替代 p53 免疫组化评估了 TP53 突变状态。突变型 p53 表达，包括过表达、完全缺失或细胞质表达，与野生型模式区分开来。对临床病理参数、其他关键生物标志物和生存分析进行了统计学关联。在所有 126 例 ESC 和 200 例 EEC3 中的 47 例（23.5%）中观察到 p53 突变型免疫组化。与 p53 野生型 EEC3 相比，ESC 和 p53 突变型 EEC3 的预后不良（风险比=2.37，95%置信区间=1.48-3.80，P=0.003，风险比=2.19，95%置信区间=1.16-4.12，P=0.016）在调整年龄、分期、中心和存在淋巴血管侵犯的多变量分析中。在多变量分析中，ESC 和 p53 突变型 EEC3 的生存无显著差异。此外，当排除错配修复（MMR）缺陷病例时，p53 突变型 EEC3 和 ESC 在单变量生存分析中几乎完全重叠，这表明同时存在 MMR 缺陷和 TP53 突变的 EEC3 更符合 MMR 状态。在 PTEN 和 p16 表达状态方面，p53 突变型 MMR 功能正常的 EEC3 和 ESC 之间仍存在显著差异。p53 突变型、MMR 功能正常的 EEC3 和 ESC 的生存与 p53 野生型 EEC3 显著不同，这证明了目前非靶向标准治疗的类似治疗是合理的。尽管如此，由于生物学差异，应继续进行单独分类，这些差异将对未来的靶向治疗变得重要。
