转移性结直肠癌中KRAS突变状态的临床病理相关性

Clinical-Pathological Correlation of KRAS Mutation Status in Metastatic Colorectal Adenocarcinoma.

作者信息

Ribeiro Karen Bento, Ribeiro Karoline Bento, Feres Omar, da Rocha Jose Joaquim Ribeiro, Rapatoni Liane, Garcia Sergio Britto, Silva Alfredo Ribeiro, da Silva Castro Perdona Gleici, de Souza Hayala Cristina Cavenague, Santillan Saul Isaac Garrido, de Oliveira Harley Francisco, da Cunha Tirapelli Daniela Pretti, Peria Fernanda Maris

机构信息

Division of Clinical Oncology, School of Medicine of Ribeirao Preto, University of Sao Paulo (Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo-FMRP-USP), Sao Paulo (SP), Brazil.

Internal Medicine, Federal University of Triangulo Mineiro (Universidade Federal do Triangulo Mineiro - UFTM), Minas Gerais (MG), Brazil.

出版信息

World J Oncol. 2013 Oct;4(4-5):179-187. doi: 10.4021/wjon719w. Epub 2013 Sep 27.

DOI:10.4021/wjon719w

PMID:29147353

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5649925/

Abstract

BACKGROUND

KRAS gene mutations play an important role in the carcinogenesis of colorectal tumors. However, studies that have assessed the association between KRAS gene mutation status and disease characteristics report conflicting results. To assess KRAS gene status (mutated or wild-type) and its association with the clinical, epidemiological, and histopathological features of metastatic colorectal adenocarcinoma as well its association with clinical outcomes.

METHODS

Cross-sectional descriptive study in which clinical and histopathological data were collected from the medical records of 65 patients diagnosed with metastatic colorectal adenocarcinoma at the Clinical Oncology Service of the Teaching Hospital of the School of Medicine of Ribeirao Preto, University of Sao Paulo (Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo -HCFMRP-USP) between 2005 and 2012 and analyzed based on their KRAS gene status.

RESULTS

KRAS gene mutations were found in 49.2% of the tumors, and G/A (25.5%) and Gly12Asp (34.37%) were the most frequent mutations. Among the investigated clinical features (gender, ECOG (Eastern Cooperative Oncology Group), histology, degree of cell differentiation, lymph node ratio, primary tumor site, staging, presence of synchronous metastasis, lung metastasis, and liver metastasis), the association between age less than 65 years with KRAS mutation was statistically significant (P = 0.046). KRAS mutation status did not exhibit a significant correlation with the overall survival of the patients (P = 0.078); however, the cases with KRAS mutation exhibited shorter survival. In the multivariate analysis, synchronous metastasis (P = 0.03) and liver metastasis (P = 0.008) behaved as independent factors of poor prognosis relative to the overall survival of the patients.

CONCLUSION

The KRAS mutation status did not exhibit prognostic value in the investigated sample. Among the older patients (> 65 years old), wild-type KRAS was more frequently observed compared to mutated KRAS.

摘要

背景

KRAS基因突变在结直肠肿瘤的致癌过程中起重要作用。然而，评估KRAS基因突变状态与疾病特征之间关联的研究报告结果相互矛盾。旨在评估KRAS基因状态（突变型或野生型）及其与转移性结直肠腺癌的临床、流行病学和组织病理学特征的关联，以及其与临床结局的关联。

方法

进行横断面描述性研究，从2005年至2012年在圣保罗大学里贝朗普雷图医学院教学医院临床肿瘤服务部（里贝朗普雷图医学院临床医院，圣保罗大学-HCFMRP-USP）诊断为转移性结直肠腺癌的65例患者的病历中收集临床和组织病理学数据，并根据其KRAS基因状态进行分析。

结果

在49.2%的肿瘤中发现KRAS基因突变，其中G/A（25.5%）和Gly12Asp（34.37%）是最常见的突变。在所研究的临床特征（性别、东部肿瘤协作组体能状态评分（ECOG）、组织学、细胞分化程度、淋巴结比例、原发肿瘤部位、分期、同时性转移的存在、肺转移和肝转移）中，年龄小于65岁与KRAS突变之间的关联具有统计学意义（P = 0.046）。KRAS突变状态与患者的总生存期无显著相关性（P = 0.078）；然而，KRAS突变的病例生存期较短。在多变量分析中，相对于患者的总生存期，同时性转移（P = 0.03）和肝转移（P = 0.008）是预后不良的独立因素。