Tumors on the far left and the most resistant on the far right. Tumor characteristics including KRAS mutation status as well as EGFR expression and phosphorylation levels, have been reported previously. No EGFR sensitizing-mutations were found in any of these tumors and there was no correlation of KRAS mutation with erlotinib response in pancreatic tumors. EGFR negative tumors tended to cluster on the right side of the map, indicating that they were more resistant to erlotinib. However, in EGFR-positive tumors we saw little association between erlotinib sensitivity and EGFR expression. Instead, we found that in these pancreatic tumors, as Mig6 expression increased, tumors exhibited a more erlotinib-resistant phenotype. For example, the erlotinib-resistant tumor PANC420 expressed markedly higher Mig6 than the erlotinib-sensitive tumor PANC410, even though they expressed comparable amounts of EGFR protein. In keeping with their Mig6 expression status, PANC410 displayed heavy EGFR phosphorylation whereas PANC420 harbored no detectable EGFR phosphorylation. Interestingly, in the 3 erlotinib-resistant pancreatic tumors studied that displayed significantly lower Mig6 expression, IHC labeling revealed that 2 of these 3 xenograft lines did not express EGFR. To investigate whether relative levels of Mig6 and EGFR expression correlate with the clinical drug response to anti-EGFR TKIs, we examined Mig6 and EGFR expression immunohistochemically and in blinded fashion on tissues from a cohort of lung cancer patients who had previously been treated 895519-90-1 supplier prospectively with gefitinib alone. Mig6 Daucosterol manufacturer cytoplasmic expression and EGFR membranous expression were analyzed in tumor cells using a score calculated intensity multiplied by extension of expression. Expression ratios were calculated as Mig6 expression/EGFR expression. We grouped the patients with positive EGFR staining in low or high Mig6/EGFR ratio groups using the number close to median as the cutoff. Our data showed that the 2 patients who had partial response were exclusively in the low ratio group, with ratios of 0 and 0.14. In addition, patients with lower Mig6/EGFR ratio have significant better outcome than the rest of the patients. patients have combined PR and stable disease $6 months in the low ratio group, but this
