错配修复蛋白异质性染色的结直肠癌临床病理特征和预后

IF 3.2 2区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY
Xian Zhang, Yu-Jue Wang, Lin-Yong Sun, Yin-Xia Tu, Yue Li, Dan Jiang
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引用次数: 0

摘要

背景:关于结直肠癌错配修复蛋白异源染色的数据很少:本研究旨在提高对带有异源性错配修复蛋白染色的结直肠癌的临床病理特征和预后的认识:单中心回顾性观察研究:本研究于2014年至2018年在中国的一家三级转诊中心进行:主要结果指标:分析临床病理和分子特征以及生存结果:在6721例结直肠癌中,共有151例(2.2%)至少一种错配修复蛋白出现异质性染色,其中腺内异质性是最常见的模式(89.4%)。异源性MLH1染色与远处转移显著相关(p = 0.03),而异源性MSH2染色与左侧(p = 0.03)和pT分期较早的肿瘤相关(p = 0.02)。微卫星不稳定性高、KRAS和BRAF突变率分别为12.6%、47.3%和3.4%。微卫星不稳定性高与较高的腺内 MSH6 异质性频率(p < 0.001)和 MSH6 表达水平下降(< 27.5%,p = 0.01)显著相关。BRAF突变与腺内异质性和克隆异质性并存(p = 0.003)和PMS2表达水平下降(p = 0.01)相关。多变量分析显示,无进展生存期与肿瘤分期(p = 0.003)、基质部分(p = 0.004)和异质性 PMS2 染色(p = 0.02)显著相关。总生存率与肿瘤分期(p = 0.006)和BRAF突变(p = 0.01)有关:本研究的局限性包括:未检测 MLH1 启动子甲基化和错配修复基因突变,研究为回顾性设计,与错配修复缺陷型和错配修复熟练型结直肠癌直接比较的相关数据不足:结论:结直肠癌中的异源性错配修复蛋白染色与肿瘤位置、分期、微卫星不稳定性、BRAF突变和预后有明显的关联。建议报告MSH6异质性,因为它可能预示着微卫星不稳定性高。参见视频摘要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Clinicopathological Characteristics and Outcomes of Colorectal Cancer With Heterogenous Staining of Mismatch Repair Protein.

Background: Scant data are available on heterogenous staining of mismatch repair protein in colorectal cancer.

Objective: This study aimed to improve insights into clinicopathologic features and prognosis of colorectal cancer harboring heterogenous mismatch repair protein staining.

Design: A single-center retrospective observational study.

Setting: This study was conducted in a tertiary referral center in China between 2014 and 2018.

Patients: Colorectal cancers with heterogenous staining of mismatch repair protein were included.

Main outcomes measures: Clinicopathologic and molecular features, and survival outcomes were analyzed.

Results: A total of 151 out of 6721 colorectal cancers (2.2%) exhibited heterogenous staining for at least one mismatch repair protein, with intraglandular heterogeneity being the most common pattern (89.4%). Heterogenous MLH1 staining was significantly associated with distant metastasis (p = 0.03), while heterogenous MSH2 staining was associated with left-sided (p = 0.03) and earlier pT stage tumors (p = 0.02). The rates of microsatellite instability-high, KRAS and BRAF mutation were 12.6%, 47.3% and 3.4%, respectively. Microsatellite instability-high was significantly associated with higher intraglandular MSH6 heterogeneity frequency (p < 0.001) and decreased MSH6 expression level (< 27.5%, p = 0.01). BRAF mutation was associated with the coexistence of intraglandular and clonal heterogeneity (p = 0.003) and decreased PMS2 expression level (p = 0.01). Multivariable analysis revealed that progression-free survival was significantly associated with tumor stage (p = 0.003), stroma fraction (p = 0.004), and heterogenous PMS2 staining (p = 0.02). Overall survival was linked to tumor stage (p = 0.006) and BRAF mutation (p = 0.01).

Limitations: The limitations of this study include the absence of testing for MLH1 promoter methylation and mismatch repair gene mutations, its retrospective design, and insufficient data related to direct comparison with deficient mismatch repair and proficient mismatch repair colorectal cancer.

Conclusions: Heterogenous mismatch repair protein staining in colorectal cancer exhibits distinct associations with tumor location, stage, microsatellite instability, BRAF mutation and prognosis. It is recommended to report MSH6 heterogeneity as it may indicate microsatellite instability-high. See Video Abstract.

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来源期刊
CiteScore
4.50
自引率
7.70%
发文量
572
审稿时长
3-8 weeks
期刊介绍: Diseases of the Colon & Rectum (DCR) is the official journal of the American Society of Colon and Rectal Surgeons (ASCRS) dedicated to advancing the knowledge of intestinal disorders by providing a forum for communication amongst their members. The journal features timely editorials, original contributions and technical notes.
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