Low-grade and early-stage endometrioid endometrial carcinomas (EECs) have an overall good prognosis but biomarkers identifying patients at risk of relapse are still lacking. Recently, CTNNB1 exon 3 mutation has been identified as a potential risk factor of recurrence in these patients. We evaluate the prognostic value of CTNNB1 mutation in a single-centre cohort of 218 low-grade, early-stage EECs, and the correlation with beta-catenin and LEF1 immunohistochemistry as candidate surrogate markers. CTNNB1 exon 3 hotspot mutations were evaluated by Sanger sequencing. Immunohistochemical staining of mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6), p53, beta-catenin, and LEF1 was performed in representative tissue microarrays. Tumours were also reviewed for mucinous and squamous differentiation, and MELF pattern. Nineteen (8.7%) tumours harboured a mutation in CTNNB1 exon 3. Nuclear beta-catenin and LEF1 were significantly associated with CTNNB1 mutation, showing nuclear beta-catenin a better specificity and positive predictive value for CTNNB1 mutation. Tumours with CTNNB1 exon 3 mutation were associated with reduced disease-free survival (p = 0.010), but no impact on overall survival was found (p = 0.807). The risk of relapse in tumours with CTNNB1 exon 3 mutation was independent of FIGO stage, tumour grade, mismatch repair protein expression, or the presence of lymphovascular space invasion. CTNNB1 exon 3 mutation has a negative impact on disease-free survival in low-grade, early-stage EECs. Nuclear beta-catenin shows a higher positive predictive value than LEF1 for CTNNB1 exon 3 mutation in these tumours.

Graphical abstract

中文翻译：

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CTNNB1突变在低级别、早期子宫内膜样癌中的临床病理学特征和预后意义

低级别和早期子宫内膜样子宫内膜癌 (EEC) 总体预后良好，但仍缺乏识别有复发风险的患者的生物标志物。最近，CTNNB1外显子 3 突变已被确定为这些患者复发的潜在危险因素。我们评估了CTNNB1突变在 218 个低级别、早期 EEC 的单中心队列中的预后价值，以及与 β-连环蛋白和 LEF1 免疫组织化学作为候选替代标志物的相关性。CTNNB1通过 Sanger 测序评估外显子 3 热点突变。在代表性组织微阵列中进行错配修复蛋白（MLH1、PMS2、MSH2 和 MSH6）、p53、β-连环蛋白和 LEF1 的免疫组织化学染色。还审查了肿瘤的粘液性和鳞状分化，以及 MELF 模式。19 个 (8.7%) 肿瘤在CTNNB1外显子 3 中存在突变。核 β-catenin 和 LEF1 与CTNNB1突变显着相关，表明核 β-catenin 对CTNNB1突变具有更好的特异性和阳性预测价值。CTNNB1外显子 3 突变的肿瘤与无病生存期降低相关（p  = 0.010），但未发现对总生存期的影响（p  = 0.807）。CTNNB1外显子 3 突变肿瘤的复发风险与FIGO 分期、肿瘤分级、错配修复蛋白表达或淋巴血管间隙侵犯的存在无关。CTNNB1外显子 3 突变对低级别早期 EEC 的无病生存有负面影响。对于这些肿瘤中的CTNNB1外显子 3 突变，核 β-连环蛋白显示出比 LEF1 更高的阳性预测值。

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