The prognostic values of EGFR expression and KRAS mutation in patients with synchronous or metachronous metastatic colorectal cancer.
The prognostic values of EGFR expression and KRAS mutation in patients with synchronous or metachronous metastatic colorectal cancer.
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DOI：
10.1186/1471-2407-13-599
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发表时间：
2013-12-13
期刊：
影响因子：
3.8
通讯作者：
Wang JY
中科院分区：
文献类型：
--
作者：
Huang CW;Tsai HL;Chen YT;Huang CM;Ma CJ;Lu CY;Kuo CH;Wu DC;Chai CY;Wang JY
表皮生长因子受体(EGFR)/RAS/RAF/MEK/MAPK通路是结直肠癌(CRC)发生、侵袭和转移的重要通路。我们进行了一项回顾性研究，旨在根据同步或异时状态确定转移性 CRC (mCRC) 患者中 EGFR 表达和 KRAS 突变的预后价值。对2002年10月至2012年3月205例转移性结直肠癌患者进行回顾性分析； 98 人被发现患有异时 mCRC，而 107 人被发现患有同步 mCRC。通过 IHC（免疫组织化学）分析测定 EGFR 表达，并将其分类为 1+（弱强度）、2+（中等强度）和 3+（强强度）。从冷冻的原代 CRC 组织中分离出基因组 DNA，并进行 KRAS 直接测序。根据EGFR表达和KRAS突变状态回顾性研究这些mCRC患者的临床病理特征。此外，我们分析了这些患者中 EGFR 表达和 KRAS 突变的预后价值。在 205 名 mCRC 患者中，对 167 名患者的 EGFR 表达进行了分析，其中 140 名患者 (83.8%) 发现 EGFR 表达阳性。对 205 名患者进行了 KRAS 突变研究，其中 88 名患者 (42.9%) 发现了突变。在异时性 mCRC 患者中，EGFR 阳性表达与肿瘤的高分化和中分化 (P = 0.028)、较差的无病生存 (DFS) (P < 0.001) 和总生存 (OS) (P < 0.001) 显着相关。此外，EGFR阳性表达是异时性mCRC患者DFS（P = 0.006，HR：4.012，95％CI：1.130-8.445）和OS（P = 0.028，HR：3.090，95％CI：1.477-10.900）的显着独立预后因素。 KRAS 突变状态与异时性 mCRC 患者的 DFS 和 OS 没有显着相关；同样，KRAS 突变状态在同步 mCRC 患者的无进展生存期 (PFS) 和 OS 方面没有显着差异（均 P>0.05）。本研究表明，EGFR 表达仅对异时性 mCRC 患者具有预后价值。然而，KRAS 突变对于异时或同步 mCRC 患者没有预后价值。
The epidermal growth factor receptor (EGFR)/RAS/RAF/MEK/MAPK pathway is an important pathway in the carcinogenesis, invasion and metastasis of colorectal cancers (CRCs). We conducted a retrospective study to determine the prognostic values of EGFR expression and KRAS mutation in patients with metastatic CRC (mCRC) based on synchronous or metachronous status. From October 2002 to March 2012, 205 patients with mCRC were retrospectively analyzed; 98 were found to have metachronous mCRC while 107 were found to have synchronous mCRC. The EGFR expressions were determinate by IHC (immunohistochemistry) analysis and categorized 1+ (weak intensity), 2+ (moderate intensity), and 3+ (strong intensity). Genomic DNA was isolated from frozen primary CRC tissues and direct sequencing of KRAS was performed. The clinicopathological features of these mCRC patients were retrospectively investigated according to EGFR expression and KRAS mutation status. Moreover, we analyzed the prognostic values of EGFR expression and KRAS mutation among these patients. Of the 205 patients with mCRC, EGFR expression was analyzed in 167 patients, and positive EGFR expression was noted in 140 of those patients (83.8%). KRAS mutation was investigated in 205 patients and mutations were noted in 88 of those patients (42.9%). In patients with metachronous mCRC, positive EGFR expression was significantly correlated with well-and moderately-differentiated tumors (P = 0.028), poorer disease-free survival (DFS) (P < 0.001), and overall survival (OS) (P < 0.001). Furthermore, positive EGFR expression was a significant independent prognostic factor of DFS (P = 0.006, HR: 4.012, 95% CI: 1.130–8.445) and OS (P = 0.028, HR: 3.090, 95% CI: 1.477–10.900) in metachronous mCRC patients. KRAS mutation status was not significantly related to DFS and OS of patients with metachronous mCRC; likewise, KRAS mutation status was not significantly different in the progression-free survival (PFS) and OS of patients with synchronous mCRC (all P > 0.05). The present study demonstrated that EGFR expression has prognostic value only for patients with metachronous mCRC. However, KRAS mutation did not have prognostic value in patients with metachronous or synchronous mCRC.
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