Introduction: Colorectal cancer (CRC) is the third most frequent malignancy and the second cause of cancer-related death worldwide. CRC is characterized by morphologic and biological heterogeneity, and molecular profiling is required to select appropriate treatment in the metastatic setting. Mutations inKRASare detected in approximately 40% of CRCs, with prognostic and predictive value, and with the most frequent being p.G12D. Nonetheless, there are few data on the morphologic features inKRAS-mutated CRCs. Materials and Methods: We retrospectively collected clinicopathological features and molecular profiles of CRCs in a multicenter cohort. Results: A total of 2816 patients from 12 centers were included.KRASmutation was found in 47.4% of cases;Gly12Aspwas detected in 23.9%, with different mutation frequencies between centers. Clinicohistological features associated withGly12Aspmutation included younger patient age (≤70 years of age), higher prevalence in males (58.6%), NOS histotype (87.1%), low pathologic grade (73.9%), high grade budding—Bd3 (43.8%), and tumoral lympho-vascular invasion (68.9%). Conclusions: Recent data have pinpointed the prognostic and predictive value ofGly12Aspmutation, and our results contribute to understanding its biology, with particular focus on peculiar clinicopathological features. Moreover, we found significant differences in pathology reports and assays for molecular profiling in different centers, which can affect a standardized therapeutic approach in CRC.
引言:结直肠癌(CRC)是全球第三大常见恶性肿瘤,也是癌症相关死亡的第二大原因。CRC具有形态学和生物学异质性特征,在转移性治疗中需要通过分子谱分析来选择合适的治疗方案。约40%的CRC病例中检测到KRAS基因突变,这些突变具有预后和预测价值,其中最常见的是p.G12D突变。然而,关于KRAS突变型CRC形态学特征的数据仍然有限。材料与方法:我们回顾性收集了一个多中心队列中CRC的临床病理特征和分子谱数据。结果:共纳入来自12个中心的2816例患者。47.4%的病例检测到KRAS突变;其中23.9%检测到Gly12Asp突变,不同中心间的突变频率存在差异。与Gly12Asp突变相关的临床病理特征包括:患者年龄较轻(≤70岁)、男性患病率较高(58.6%)、非特殊类型组织学亚型(87.1%)、低病理分级(73.9%)、高级别出芽(Bd3级,43.8%)以及肿瘤淋巴血管侵犯(68.9%)。结论:最新数据已明确Gly12Asp突变的预后和预测价值,我们的研究结果有助于理解其生物学特性,特别关注其独特的临床病理特征。此外,我们发现不同中心的病理报告和分子谱检测方法存在显著差异,这可能影响CRC标准化治疗策略的实施。