Abstract
BackgroundThe 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.MethodsFrom 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.ResultsOf 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).ConclusionsThe 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.
Highlights
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)
Disease-free survival (DFS) for patients with metachronous metastatic CRC (mCRC) was defined as the time from the date of primary treatment to the date of diagnosis for recurrence or metastatic disease or to the date of the last follow-up
Progress-free survival (PFS) for patients with synchronous mCRC was defined as the time from the date of primary treatment to the date of tumor progression or to the date of death from any cause, or to the date of the last follow-up
Summary
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). In Taiwan, CRC is the most common cancer type, having increased rapidly in prevalence, and the third leading cause of cancer-related death as of 2012. The prognoses of metastasis colorectal cancer (mCRC) have improved in the past decade, with the median overall survival (OS) rate increasing from 12 months to more than 24 months [3,4]. These improvements are considered to be a result of the development of combinations of standard chemotherapy, including fluoropyrimidine/folinic acid, irinotecan (FOLFIRI), and oxaliplatin (FOLFOX), and the introduction of new targeted biological agents such as cetuximab, panitumumab, and bevacizumab
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