摩洛哥 414 例转移性结直肠癌 KRAS 和 NRAS 突变状态与临床病理特征的相关性：最大的北非病例系列。
Correlation between KRAS and NRAS mutational status and clinicopathological features in 414 cases of metastatic colorectal cancer in Morocco: the largest North African case series.
机构信息
Pathology department, National Institute of Oncology, Rabat, Morocco.
Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat, Morocco.
出版信息
BMC Gastroenterol. 2023 Jun 5;23(1):193. doi: 10.1186/s12876-023-02694-7.
BACKGROUND
Advances in molecular biology have improved understanding of the molecular features of carcinogenesis and progression of colorectal cancer. It is clear that the efficacy of anti-EGFR depends upon the RAS mutational status, since any mutation in RAS is associated with resistance to anti-EGFR therapy. The aim of this study is to report the largest North African description of KRAS and NRAS status in metastatic colorectal cancer and to describe the association of these mutations with clinicopathological characteristics.
METHODS
This is a prospective study of all consecutive unselected metastatic colorectal cancer samples, collected from the Laboratory of Pathology at the National Institute of Oncology of Rabat, Morocco, from January 1st 2020 to December 31st 2021. The molecular analysis was performed on the Idylla™ platform (fully automated real-time polymerase chain reaction-based assay) for KRAS and NRAS mutations in exons 2, 3 and 4. These mutations were correlated to gender, primary tumor site, histological type and degree of differentiation of tumor using adequate statistical methods.
RESULTS
Four hundred fourteen colorectal tumors were screened for KRAS and NRAS mutations. These mutations occurred in 51.7% of tumors for KRAS (mainly in exon 12) and in 3% of tumors for NRAS. There was a significant correlation between NRAS mutation and age of colorectal patients in this study. The low rate of invalid RAS tests (1.7% for KRAS and 3.1% for NRAS) was certainly obtained due to the strict respect of pre-analytical factors such as cold ischemia time and formalin fixation.
CONCLUSION
We report the largest North African analysis of NRAS and KRAS status in colorectal metastatic patients. This study showed the ability in low middle income countries to perform a high rate of valid tests and the unusual trend towards older patients for NRAS mutations.
背景
分子生物学的进步提高了对结直肠癌发生和进展的分子特征的理解。很明显，抗 EGFR 的疗效取决于 RAS 突变状态，因为 RAS 中的任何突变都与抗 EGFR 治疗的耐药性相关。本研究的目的是报告北非最大的转移性结直肠癌中 KRAS 和 NRAS 状态的描述，并描述这些突变与临床病理特征的关系。
方法
这是一项对摩洛哥拉巴特国家肿瘤学研究所病理学实验室收集的所有连续未选择的转移性结直肠癌样本的前瞻性研究，时间为 2020 年 1 月 1 日至 2021 年 12 月 31 日。分子分析在 Idylla™ 平台上进行（完全自动化的实时聚合酶链反应检测），用于检测 KRAS 和 NRAS 外显子 2、3 和 4 的突变。使用适当的统计方法，将这些突变与性别、原发肿瘤部位、组织学类型和肿瘤的分化程度相关联。
结果
对 414 例结直肠肿瘤进行了 KRAS 和 NRAS 突变筛查。KRAS 突变发生在 51.7%的肿瘤中（主要在外显子 12），NRAS 突变发生在 3%的肿瘤中。在这项研究中，NRAS 突变与结直肠患者的年龄之间存在显著相关性。由于严格遵守冷缺血时间和福尔马林固定等分析前因素，KRAS 的无效 RAS 检测率（1.7%）和 NRAS 的无效 RAS 检测率（3.1%）非常低。
结论
我们报告了北非最大的转移性结直肠癌患者 NRAS 和 KRAS 状态分析。本研究显示了在中低收入国家进行高比例有效检测的能力，以及 NRAS 突变在老年患者中罕见的趋势。
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