Orlandi Elena, Giuffrida Mario, Trubini Serena, Luzietti Enrico, Ambroggi Massimo, Anselmi Elisa, Capelli Patrizio, Romboli Andrea
Department of Oncology-Hematology, Piacenza General Hospital, 29121 Piacenza, Italy.
Department of General Surgery, Piacenza General Hospital, 29121 Piacenza, Italy.
Diagnostics (Basel). 2024 May 12;14(10):1001. doi: 10.3390/diagnostics14101001.
Microsatellite Instability (MSI-H) occurs in approximately 15% of non-metastatic colon cancers, influencing patient outcomes positively compared to microsatellite stable (MSS) cancers. This systematic review focuses on the prognostic significance of KRAS, NRAS, and BRAF mutations within MSI-H colon cancer. Through comprehensive searches in databases like MEDLINE, EMBASE, and others until 1 January 2024, we selected 8 pertinent studies from an initial pool of 1918. These studies, encompassing nine trials and five observational studies involving 13,273 patients, provided insights into disease-free survival (DFS), survival after recurrence, and overall survival. The pooled data suggest that while KRAS and BRAF mutations typically predict poorer outcomes in MSS colorectal cancer, their impact is less pronounced in MSI contexts, with implications varying across different stages of cancer and treatment responses. In particular, adverse effects of these mutations manifest significantly upon recurrence rather than affecting immediate DFS. Our findings confirm the complex interplay between genetic mutations and MSI status, emphasizing the nuanced role of MSI in modifying the prognostic implications of KRAS, NRAS, and BRAF mutations in colon cancer. This review underscores the importance of considering MSI alongside mutational status in the clinical decision-making process, aiming to tailor therapeutic strategies more effectively for colon cancer patients.
微卫星不稳定性（MSI-H）在约15%的非转移性结肠癌中出现，与微卫星稳定（MSS）的癌症相比，对患者预后有积极影响。本系统评价聚焦于MSI-H结肠癌中KRAS、NRAS和BRAF突变的预后意义。通过在MEDLINE、EMBASE等数据库中进行全面检索直至2024年1月1日，我们从最初的1918项研究中筛选出8项相关研究。这些研究包括9项试验和5项观察性研究，涉及13273例患者，提供了无病生存期（DFS）、复发后生存期和总生存期方面的见解。汇总数据表明，虽然KRAS和BRAF突变通常预示MSS结直肠癌预后较差，但在MSI情况下其影响不那么明显，在癌症的不同阶段和治疗反应中影响各异。特别是，这些突变的不良影响在复发时显著显现，而非影响即刻DFS。我们的研究结果证实了基因突变与MSI状态之间的复杂相互作用，强调了MSI在改变KRAS、NRAS和BRAF突变对结肠癌预后影响方面的细微作用。本综述强调了在临床决策过程中将MSI与突变状态一并考虑的重要性，旨在更有效地为结肠癌患者量身定制治疗策略。
