Department of Surgery, Teikyo University School of Medicine, Kaga, Itabashi-ku, Tokyo, Japan.
Dis Colon Rectum. 2011 Sep;54(9):1170-8. doi: 10.1097/DCR.0b013e31821d37a3.
KRAS status is a useful predictive marker for anti-epidermal growth factor receptor antibody therapy.
This study aimed to examine the concordance rate of KRAS mutation status between corresponding primary and metastatic colorectal cancer lesions, and also among multiple metastatic tumors. Furthermore, we examined the heterogeneity of KRAS mutations with respect to discordant KRAS status between primary and metastatic tumors.
This study was retrospective in design.
Forty-three patients with primary tumors and 113 metastatic tumors were studied.
The KRAS mutational status was determined by the peptide nucleic acid clamp real-time polymerase chain reaction TaqMan assay. We also performed sequencing analysis to validate the KRAS mutational status. When KRAS status differed between primary and metastatic tumors, we examined the heterogeneity of KRAS status within individual primary tumors by microdissecting multiple samples in each patient.
The frequency of KRAS mutations in primary tumors was 34.9%. A high concordance rate of KRAS (88.4-91.7%) mutations was observed between primary and metastatic tumors. All 5 cases (11.6%) with discordant KRAS status had heterogeneous KRAS status in primary tumors. However, in 10 concordant cases all microdissected areas showed an identical KRAS mutational status within each patient. The KRAS mutational statuses in all multiple liver and/or lung metastatic tumors were the same as those of the primary tumor.
We could not validate KRAS status in microdissected samples by the direct sequence method that was used in the present study, because the quantity of DNA was not sufficient to perform direct sequencing.
KRAS status in a primary site may be used for selecting patients who would benefit from anti-epidermal growth factor receptor therapy. However, KRAS status can be heterogeneous within a primary tumor, and thus different parts of such tumors should be examined for KRAS status to correctly predict the KRAS status in metastatic lesions.
KRAS 状态是抗表皮生长因子受体抗体治疗的有用预测标志物。
本研究旨在检测原发和转移性结直肠癌病灶之间、多个转移灶之间 KRAS 突变状态的一致性，并检测 KRAS 突变状态在原发和转移灶 KRAS 状态不一致时的异质性。
本研究为回顾性设计。
43 例原发肿瘤患者和 113 例转移肿瘤患者。
KRAS 突变状态通过肽核酸夹实时聚合酶链反应 TaqMan 法确定。我们还进行了测序分析以验证 KRAS 突变状态。当原发和转移肿瘤的 KRAS 状态不同时，我们通过在每个患者的多个样本中进行微切割，检测个体原发肿瘤中 KRAS 状态的异质性。
原发肿瘤 KRAS 突变频率为 34.9%。原发和转移肿瘤之间 KRAS（88.4%-91.7%）突变具有高度一致性。所有 5 例（11.6%） KRAS 状态不一致的病例在原发肿瘤中均存在 KRAS 状态异质性。然而，在 10 例一致性病例中，每个患者的所有微切割区域均显示出相同的 KRAS 突变状态。所有多个肝和/或肺转移瘤的 KRAS 突变状态与原发肿瘤相同。
由于本研究中使用的直接测序方法无法验证微切割样本中的 KRAS 状态，因为 DNA 数量不足以进行直接测序。
原发部位的 KRAS 状态可用于选择受益于抗表皮生长因子受体治疗的患者。然而，原发肿瘤内的 KRAS 状态可能存在异质性，因此应检查肿瘤的不同部位以确定 KRAS 状态，从而正确预测转移病灶中的 KRAS 状态。
