Rodríguez Marta Rada, Biedma Bárbara Angulo, Rodríguez Pérez Irene, Romeo Javier Azúa
Department of Human Anatomy and Histology, Universidad de Zaragoza, Calle Pedro Cerbuna, 50009 Zaragoza, Spain.
Area of Molecular Biology, Analiza, 28008 Madrid, Spain.
Cancers (Basel). 2025 Jun 20;17(13):2071. doi: 10.3390/cancers17132071.
We retrospectively and cross-sectionally reviewed the cases of 648 patients with a histological diagnosis of colon adenocarcinoma. Of these, 166 had partial molecular studies, and 42 cases were selected based on the availability of the genetic markers targeted in this study. We analyzed the frequency of mutations in these genes, as well as their correlation with microsatellite instability (MSI).
A high mutation rate was found in the gene (52.4%). mutations were less frequent (8.9%), whereas mutations were observed in 20.8% of cases. This allowed us to identify a patient subgroup with MSI, representing 12.1% of cases. Among the 42 patients analyzed for , , , and MSI mutations, a significant association was observed between mutations and microsatellite stability, while no association was found between mutations and MSI. mutations showed a statistically significant association with MSI ( < 0.05), with the most common mutation being c.1799T > A, . The objective of this study is to demonstrate that the NGS-based method for evaluating MSI is rigorously valid compared to the results obtained using IHC and PCR.
Comprehensive NGS profiling from the start improves diagnostic efficiency by saving time, tissue, and costs compared to gene-by-gene analysis. It also enables better molecular characterization and facilitates tailored therapeutic strategies, particularly in identifying candidates for targeted therapy and immunotherapy. This approach supports efficient tumor classification based on using , , , , and as key markers, along with MSI status. We recommend that, if initial NGS is not feasible, start with analysis, then test and MSI if no mutation is found.
我们对648例经组织学诊断为结肠腺癌的患者病例进行了回顾性横断面研究。其中，166例进行了部分分子研究，基于本研究中靶向基因标记物的可获得性选择了42例病例。我们分析了这些基因中的突变频率，以及它们与微卫星不稳定性（MSI）的相关性。
在 基因中发现了较高的突变率（52.4%）。 突变频率较低（8.9%），而在20.8%的病例中观察到 突变。这使我们能够识别出一个MSI患者亚组，占病例的12.1%。在分析 的42例患者中，观察到 突变与微卫星稳定性之间存在显著关联，而 突变与MSI之间未发现关联。 突变与MSI显示出统计学显著关联（<0.05），最常见的突变是c.1799T>A， 。本研究的目的是证明与使用免疫组化（IHC）和聚合酶链反应（PCR）获得的结果相比，基于二代测序（NGS）的MSI评估方法具有严格的有效性。
与逐个基因分析相比，从一开始就进行全面的NGS分析可节省时间、组织和成本，从而提高诊断效率。它还能够实现更好的分子特征分析，并促进定制化治疗策略，特别是在识别靶向治疗和免疫治疗候选者方面。这种方法支持基于使用 、 、 、 和 作为关键标记物以及MSI状态进行有效的肿瘤分类。我们建议，如果最初的NGS不可行，则从 分析开始，然后在未发现突变时检测 和MSI。
