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. 2025 Mar 20;56(2):434-441.
doi: 10.12182/20250360106.

[PIK3CA Somatic Mutations Are Associated With Lymph Node Metastasis in Endometrial Cancer]

[Article in Chinese]
Qingyu Shen  1   2 , Chenfan Tian  1 , Xiaoxiao Luo  1 , Fan Yang  1 , Peng Jiang  1 , Yunfeng Zheng  1
Affiliations

[PIK3CA Somatic Mutations Are Associated With Lymph Node Metastasis in Endometrial Cancer]

[Article in Chinese]
Qingyu Shen et al. Sichuan Da Xue Xue Bao Yi Xue Ban. .

Abstract
in English, Chinese

Objective: To investigate the expression levels and mutation status of phosphatidylinositol-4, 5-bisphosphate3-kinase catalytic subunit alpha (PIK3CA) in endometrial cancer (EC) and evaluate its association with lymph node metastasis in EC.

Methods: We retrosepctively collected and analyzed EC genetic mutation testing data submitted to the Molecular Detection Center, The First Affiliated Hospital of Chongqing Medical University between July 2020 and June 2022. The mutation rate of PIK3CA gene was calculated based on the sequencing results of EC patients, and the correlation between PIK3CA mutations and clinical pathological parameters, as well as protein expression consistency, was analyzed accordingly.

Results: A total of 97 EC patients were enrolled in this study, and PIK3CA mutations were identified in approximately 48.5% (47 out of 97 cases). The rate of lymph node metastasis in patients with PIK3CA mutations was higher than that in patients with wild-type PIK3CA (21.3% vs. 6.0%, P = 0.027). Findings from univariate and multivariate logistic analyses indicated that histological subtype Ⅱ (odds ratio [OR] = 5.51; 95% CI, 1.08-28.06; P = 0.040), positive result for lymphovascular space invasion (LVSI) (OR = 7.96; 95% CI, 1.37-46.44; P = 0.021), and PIK3CA mutation (OR = 8.58; 95% CI, 1.51-48.84; P = 0.015) were independent risk factors for lymph node metastasis in EC. In addition, the receiver-operating characteristic (ROC) curves demonstrated that the combined use of clinicopathological parameters and PIK3CA mutations could more accurately predict lymph node metastasis in EC, with an area under the curve of 0.824 (95% CI, 0.678-0.970). It is noteworthy that there was a high consistency between PIK3CA mutations and its protein expression, and EC patients with positive expression of PIK3CA protein had a higher rate of lymph node metastasis (53.8% vs. 9.1%, P = 0.078).

Conclusion: PIK3CA somatic mutations are strongly correlated with lymph node metastasis in EC.

目的: 探讨磷脂酰肌醇-4,5-二磷酸3-激酶催化亚基α（phosphatidylinositol-4, 5-bisphosphate3-kinase catalytic subunit alpha, PIK3CA）在子宫内膜癌（endometrial cancer, EC）中的表达水平和突变情况，并分析其与EC淋巴结转移之间的联系。

方法: 回顾性收集2020年7月–2022年6月期间提交至重庆医科大学附属第一医院分子检测中心实验室的EC突变基因检测数据，基于EC患者的测序结果计算PIK3CA基因突变率，分析PIK3CA突变与EC临床病理参数之间的相关性，以及与蛋白表达的一致性。

结果: 本研究共纳入EC患者97例，其中PIK3CA突变率约为48.5%（47/97）。PIK3CA突变型患者的淋巴结转移率高于野生型患者（21.3% vs. 6.0%，P=0.027）。单因素与多因素logistic分析结果显示，组织学亚型Ⅱ型〔比值比（odds ratio, OR）=5.51，95%置信区间（confidence interval, CI）：1.08～28.06，P=0.040〕，淋巴脉管浸润（lymphovascular space invasion, LVSI）阳性（OR=7.96， 95%CI：1.37～46.44，P=0.021）和PIK3CA突变（OR=8.58，95%CI：1.51～48.84，P=0.015）是EC淋巴结转移的独立危险因素。同时，ROC曲线显示结合临床病理参数和PIK3CA突变能更准确地预测EC淋巴结转移，曲线下面积为0.824（95%CI：0.678～0.970）。PIK3CA突变与其蛋白表达保持较高的一致性，PIK3CA蛋白阳性的EC患者具有更高的淋巴结转移率（53.8% vs. 9.1%，P=0.078）。

结论: PIK3CA突变与EC淋巴结转移密切相关。

Keywords: Endometrial carcinoma; Genetic testing; PIK3CA; TCGA molecular subtypes.

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Conflict of interest statement

利益冲突 所有作者均声明不存在利益冲突

Figures

图 1
图 1
Characterization of PIK3CA mutations in the EC patient cohorts PIK3CA基因突变在EC患者队列中的特征分析 POLEmut: POLE ultramutated; MSI-H: microsatellite instability-high; CN-L: low copy number type; CN-H: high copy number type; PTEN: phosphatase and tensin homolog; PIK3CA: phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; ARID1A: AT-rich interaction domain 1A; PIK3R1: phosphoinositide-3-kinase regulatory subunit 1; CTNNB1: catenin beta 1; ATM: ataxia telangiectasia-mutated; TP53: tumor protein p53; CTCF: CCCTC-binding factor; NSD1: nuclear receptor binding SET domain protein 1; KRAS: Kirsten rats arcomaviral oncogene homolog‌. A, Gene mutation frequency in the patient cohort (n = 97) from The First Affiliated Hospital of Chongqing Medical University (FAHCQMU); B, types and frequencies of PIK3CA gene mutations (n = 47); C, the proportion of TCGA molecular subtypes in the patient cohort (n = 47).
图 2
图 2
ROC curves of the prediction of lymph node metastasis in EC by the conbined use of PIK3CA mutation and clinical pathological parameters PIK3CA突变与临床病理参数联合预测EC淋巴结转移的ROC曲线 AUC: area under the curve; LVSI: lymphatic vessel space invasion.
图 3
图 3
Analysis of the consistency between PIK3CA mutations and protein expression, as well as their correlation with lymph node metastasis in EC PIK3CA突变与蛋白表达一致性及其与EC淋巴结转移的关系 LNM: lymph node metastasis; PIK3CA-WT: PIK3CA wild-type; PIK3CA-MT: PIK3CA mutant-type. A, The proportion of positive and negative expression of PIK3CA protein under different PIK3CA mutation statuses (PIK3CA-WT: n = 12, PIK3CA-MT: n = 12). B, Distribution of different PIK3CA mutation types in the positive (n = 13) and negative (n = 11) expression states of PIK3CA protein. C, Representative images of the tissue microarray, illustrating the overall structure (original magnification × 40) and a detailed view (original magnification × 200). D, Distribution of lymph node metastasis status in the positive (n = 13) and negative (n = 11) expression states of PIK3CA protein.
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