Department of Pathology & Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Adv Anat Pathol. 2010 Jan;17(1):23-32. doi: 10.1097/PAP.0b013e3181c6962f.
A number of studies have shown that although antiepidermal growth factor receptor (EGFR) monoclonal antibodies are effective treatments for metastatic colorectal cancer (mCRC), only patients with wild-type KRAS tumors derive clinical benefit from these therapies. The anti-EGFR monoclonal antibodies panitumumab and cetuximab are approved in the United States for treatment of mCRC refractory to chemotherapy but are not recommended for use in patients with mutations in KRAS codons 12 or 13. Similarly, panitumumab is approved for the treatment of mCRC only in patients with wild-type KRAS in Europe and Canada. It is clear that KRAS mutational analysis will become an important aspect of disease management in patients with mCRC. Consequently, it will be important for pathologists and oncologists to develop and agree on standardized KRAS testing and reporting procedures to ensure optimum patient care. Pathologists will be central to this process because of their crucial role in selecting appropriate tumor specimens for testing, choosing the molecular diagnostic laboratory to be used, assisting in the selection of a suitable KRAS test, and interpreting the results of KRAS mutational analysis. Guidelines for KRAS testing that address these and other important points of consideration have recently been proposed in the United States and the European Union.
许多研究表明，尽管抗表皮生长因子受体（EGFR）单克隆抗体是转移性结直肠癌（mCRC）的有效治疗方法，但只有 KRAS 肿瘤野生型的患者才能从这些治疗中获得临床获益。在美国，抗 EGFR 单克隆抗体帕尼单抗和西妥昔单抗被批准用于治疗对化疗耐药的 mCRC，但不建议用于 KRAS 密码子 12 或 13 突变的患者。同样，在欧洲和加拿大，帕尼单抗仅被批准用于 KRAS 野生型 mCRC 的治疗。很明显，KRAS 基因突变分析将成为 mCRC 患者疾病管理的一个重要方面。因此，病理学家和肿瘤学家制定并达成标准化的 KRAS 检测和报告程序以确保为患者提供最佳治疗至关重要。由于病理学家在选择用于检测的合适肿瘤标本、选择要使用的分子诊断实验室、协助选择合适的 KRAS 检测以及解释 KRAS 突变分析结果方面发挥着关键作用，因此他们将成为这一过程的核心。最近，美国和欧盟提出了 KRAS 检测指南，其中涉及到这些和其他重要的考虑因素。
