肥胖与子宫内膜癌微卫星不稳定性相关：一项回顾性观察研究

IF 3 3区医学 Q2 ONCOLOGY

Seminars in oncology Pub Date : 2025-02-01 DOI:10.1053/j.seminoncol.2025.01.001

Carlo Ronsini , Eleonora Braca , Mario Fordellone , Federica Zito Marino , Stefania Napolitano , Antonio Raffone , Luigi Cobellis , Pasquale De Franciscis

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引用次数: 0

摘要

目的探讨肥胖与子宫内膜癌（EC）微卫星不稳定性（Microsatellite Instability， MSI）的关系，确定哪些错配修复（mismatch repair， MMR）蛋白丢失受肥胖影响，并评估BMI与MSI概率的相关性。方法回顾性队列研究纳入2023年8月至2024年10月在坎帕尼亚大学Luigi Vanvitelli妇科肿瘤科接受治疗的89例子宫内膜癌患者，按体重指数（BMI）分层：正常体重（n = 26）、超重（n = 31）、肥胖（n = 26）和严重肥胖（n = 6）。微卫星不稳定性（MSI）通过免疫组化评估错配修复（MMR）蛋白表达：MLH1、PMS2、MSH2和MSH6来确定。如果四种MMR蛋白中至少有一种表达缺失，则认为肿瘤为MSI。建立单因素和多因素logistic回归模型来评估BMI与msi的相关性。与正常体重组（12%）和超重组（29%）相比，肥胖和严重肥胖组的MSI率（各为50%）显著高于超重组（P = .013）。肥胖和严重肥胖女性中MLH1和PMS2的表达缺失明显更高(MLH1: P = .003；PMS2: P = .014)。单因素logistic回归显示BMI与MSI呈正相关（OR 1.02, 95% CI 1.01-1.04, P = .007）。在多变量分析中，调整分级、分期、组织型和年龄，BMI与MSI保持显著正相关（OR 1.02, 95% CI 1.01-1.04, P = .048）。结论肥胖与EC中MSI存在显著相关性，尤其是影响MLH1和PMS2的表达。研究结果表明，肥胖也可能通过MMR缺乏导致EC的发展。

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Obesity correlates to the microsatellite instability of endometrial cancer: A retrospective observational study

Objective

To investigate the relationship between obesity and Microsatellite Instability (MSI) in endometrial cancer (EC), determine which mismatch repair (MMR) protein loss is influenced by obesity, and assess the correlation between BMI and MSI probability.

Methods

This retrospective cohort study included 89 endometrial cancer patients treated at the Gynaecologic oncology unit of the University of Campania “Luigi Vanvitelli” from August 2023 to October 2024, and stratified by BMI: normal weight (n = 26), overweight (n = 31), obese (n = 26), and severely obese (n = 6). Microsatellite instability (MSI) was determined through immunohistochemical assessment of mismatch repair (MMR) protein expression: MLH1, PMS2, MSH2, and MSH6. Tumors were considered MSI if at least one of the four MMR proteins showed loss of expression. Univariate and multivariate logistic regression models were constructed to evaluate the correlation between BMI and MSI

Results

89 patients were enrolled. Obese and severely obese groups showed significantly higher MSI rates (50 % each) compared to normoweight (12 %) and overweight (29 %) groups (P = .013). MLH1 and PMS2 loss of expression were significantly higher in obese and severely obese women (MLH1: P = .003; PMS2: P = .014). Univariate logistic regression showed a significant positive correlation between BMI and MSI (OR 1.02, 95 % CI 1.01–1.04, P = .007). In multivariate analysis, adjusting for grading, stage, histotype, and age, BMI maintained a significant positive correlation with MSI (OR 1.02, 95 % CI 1.01–1.04, P = .048).

Conclusions

This study demonstrates a significant association between obesity and MSI in EC, particularly affecting MLH1 and PMS2 expression. The findings suggest that obesity may contribute to EC development also through MMR deficiency.

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来源期刊

Seminars in oncology 医学-肿瘤学

CiteScore

6.60

自引率

0.00%

发文量

审稿时长

104 days

期刊介绍： Seminars in Oncology brings you current, authoritative, and practical reviews of developments in the etiology, diagnosis and management of cancer. Each issue examines topics of clinical importance, with an emphasis on providing both the basic knowledge needed to better understand a topic as well as evidence-based opinions from leaders in the field. Seminars in Oncology also seeks to be a venue for sharing a diversity of opinions including those that might be considered "outside the box". We welcome a healthy and respectful exchange of opinions and urge you to approach us with your insights as well as suggestions of topics that you deem worthy of coverage. By helping the reader understand the basic biology and the therapy of cancer as they learn the nuances from experts, all in a journal that encourages the exchange of ideas we aim to help move the treatment of cancer forward.