P59: Microsatellite unstable (MSI) colorectal cancer (CRC) is characterized by significantly increased epidermal growth factor receptor (EGFR) expression

Abstract

Introduction: EGFR over expression has been reported in multiple solid tumor malignancies including colorectal cancer and the EGFR targeted molecular therapy Cetuximab, has demonstrated significant but modest effectiveness against human CRC. Importantly, literature suggests microsatellite unstable (MSI) CRC is characterized by poor response to standard adjuvant chemotherapy compared to microsatellite stable (MSS) CRC. The purpose of our present study was to expand our analysis of differential gene expression in human CRC (Oncogene 2005 24:3657-3668) and test the hypothesis that MSI CRC is characterized by significantly increased expression of EGFR over that observed in microsatellite stable (MSS) CRC. Methods: Twenty eight human CRC cell lines including 11MSI cell lines were employed to measure EGFR protein and mRNAexpression using properly controlled Western blots and real time PCR respectively. Independently read densitometry analysis of those same Western blots and quantitative analysis of the RT PCR data was performed. Results: EGFR expression was detected by Western blot and RT PCR in each of the 28 CRC cell lines studied including the 11 MSI lines. Comparative analysis of the MSI and MSS CRC cell line results demonstrated significantly increased EGFR expression among the MSI lines over that observed in the MSS lines as measured by Western blot and RT PCR. Densitometry analysis of these same Western blots and quantitative analysis of the RT PCR data confirmed statistically significant increased EGFR expression levels among MSI vs. MSS cell lines with p values of 0.001 and 0.009 respectively. Conclusions: In summary, these novel results support our proposed hypothesis indicating MSI CRC is characterized by significantly increased EGFR expression over that observed in MSS CRC. These results suggest EGFR targeted molecular therapies may provide important alternative therapeutic strategies for MSI CRC. Based on these findings we conclude further study of EGFR over expression in MSI CRC is warranted and an expanded analysis of the mechanism(s) of increased EGFR expression in human MSI CRC is underway in our laboratory.