ABSTRACT
BACKGROUND: Overexpression of epidermal growth factor receptor (EGFR) is found in many types of neoplasms. The aim of the study was to evaluate EGFR expression in colorectal cancer (CRC) specimens and to determine whether EGFR expression correlates with clinicopathological data and overall survival. PATIENTS AND METHODS: Tissue specimens from 181 consecutive CRC patients treated at the Military Institute of Medicine in 2006-2010 were collected and examined for EGFR expression, by immunohistochemistry staining. The staining intensity and percentage of cells with membranous EGFR expression were scored and then grouped according to the parameters of the Allred Scoring system. Cutoff values were subjected to further statistical analysis. Univariate tests and a multivariate Cox proportional hazards model were used in data analysis. RESULTS: EGFR was overexpressed in 96 of 181 CRC specimens (53%). EGFR expression was not correlated with other clinicopathological variables. On univariate analysis, overexpression of EGFR, determined by PS (percentage score) (>3) and total score (sum of PS and intensity score) (>4), was associated with poor overall survival. On multivariate analysis, EGFR overexpression (PS > 3) was an independent adverse prognostic factor (hazard ratio [HR] 1.62; 95% confidence interval [CI]: 1.03-2.53). Elevated carcinoembryonic antigen (CEA) serum concentration before treatment, performance status (Word Health Organization [WHO]-2), and tumor localized in colon and liver metastases were also independent unfavorable prognostic factors. CONCLUSION: EGFR overexpression (PS > 3) in a CRC patient population was an independent adverse prognostic factor. Implementation of the Allred Scoring system criteria into clinical practice might facilitate treatment decisions in CRC patients.
ABSTRACT
BACKGROUND: CRC caused more than 600,000 estimated deaths in 2008. Dysregulated signaling through the RAS/RAF/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway due to mutations in K-Ras and B-Raf are common events in CRC. METHODS: Incidence of mutations in codons 12 and 13 of K-Ras and exons 11 and 15 of B-Raf were analyzed in amplified PCR products from primary tumors of 273 patients with CRC, and their prognostic and predictive significance was assessed. The prognostic role of clinical and pathological factors was also examined. RESULTS: K-Ras mutations were present in 89 patients (32.6%), of whom 76 (85.4%) had mutations in codon 12 and 10 (11.2%) had mutations in codon 13. B-Raf gene mutations were present in 17 patients (6.9%), of whom 6 (35.3%) had mutations in exon 15. Multivariate analysis revealed a predictive significance for K-Ras mutations with respect to time to progression in patients treated with irinotecan and oxaliplatin as first-line chemotherapy. There was no predictive significance for B-Raf gene mutation status in these patients. The following risk factors were found to affect overall survival (OS) rates: primary tumor location, lymph node involvement grade, carcinoembryonic antigen (CEA) level before treatment, and performance status according to WHO criteria. CONCLUSIONS: Based on the results of this study, K-Ras mutation status may be a suitable indicator of patient eligibility and a prognostic indicator for responsiveness to anti-EGFR therapy alone, or in combination with chemotherapy. Also, K-Ras mutation status may predict time to progression in patients treated with irinotecan and oxaliplatin.
