Equivalent Survival of p53 Mutated Endometrial Endometrioid Carcinoma Grade 3 and Endometrial Serous Carcinoma
Equivalent Survival of p53 Mutated Endometrial Endometrioid Carcinoma Grade 3 and Endometrial Serous Carcinoma
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DOI：
10.1097/pgp.0000000000000674
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发表时间：
2021-03-01
影响因子：
2.4
通讯作者：
Kobel, Martin
中科院分区：
文献类型：
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作者：
Brett, Mary Anne;Atenafu, Eshetu G.;Kobel, Martin
TP53状态是子宫内膜癌最重要的预后生物标志物。我们询问p53突变的子宫内膜是否有不同的结局，3级子宫内膜样癌（EEC3）或子宫内膜浆液性癌（ESC），后者普遍存在TP53突变。采用替代p53免疫组化技术对来自加拿大2个主要癌症中心的326例EEC3和ESC患者进行TP53突变状态评估。突变型p53表达，包括过表达、完全缺失或细胞质表达，与野生型不同。与临床病理参数、其他关键生物标志物和生存分析进行统计关联。在所有126例ESC和47/200例（23.5%）EEC3中均观察到P53突变型免疫组化。在校正了年龄、分期、中心和是否存在淋巴血管浸润的多变量分析中，与p53野生型EEC3相比，ESC和p53突变EEC3的预后较差（风险比= 2.37,95%可信区间=1.48 ~ 3.80,P = 0.003，风险比= 2.19,95%可信区间=1.16 ~ 4.12,P = 0.016）。在多变量分析中，ESC和p53突变的EEC3的生存率无显著差异。此外，当排除错配修复（MMR）缺陷病例时，p53突变的EEC3和ESC在单变量生存分析中几乎完全重叠，这表明同时携带MMR缺陷和TP53突变的EEC3的行为更符合MMR状态。p53突变的mmr熟练EEC3和ESC在PTEN和p16表达状态上仍然存在显著差异。p53突变、mmr熟练的EEC3和ESC的重叠生存期与p53野生型EEC3显著不同，这证明了与目前非靶向标准治疗类似的治疗方法是合理的。尽管如此，由于生物学差异，应该继续进行单独分类，这对未来的靶向治疗很重要。
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.