59 25.48 2 56 Male AdenoCa
Smoker 4th ND ND ND ND ND PD 2.39 4.23 3 76 Male Squamous Smoker 2nd ND ND ND ND Deletion PR 11.67+ 11.67+ 4 64 Male CP673451 AdenoCa Non-smoker 2nd Negative Negative Negative Negative Deletion NE 8.52 29.51 5 76 Female AdenoCa Non-smoker 1st Negative Negative ND Negative Normal SD 12.69 23.38 6 78 Female AdenoCa Non-smoker 1st Negative Negative Negative Negative Normal PR 20.52 21.34 check details 7 67 Male AdenoCa Smoker 2nd Negative Negative Negative Negative Normal PD 3.25 28.49 8 62 Female AdenoCa Non-smoker 1st Positive Positive Positive Negative Normal SD 40.20+ 40.20+ 9 47 Male AdenoCa Smoker 2nd ND ND ND ND ND NE 4.00 4.00 10 43 Female AdenoCa Non-smoker 2nd ND ND ND ND ND PD 2.56 2.85 11 63 Male Squamous Smoker 2nd ND ND ND ND ND PD 2.26 12.49 ND: not done; NE: non-evaluable. Protein MEK inhibitor expression analysis (Immunohistochemistry) High EGFR expressing tumors were found in 7/45 tested cases, 1/15
from the gefitinib treated group and 6/30 from the erlotinib group. Phospho-EGFRTyr1173 positivity was found in 24 (56%) cases, with similar results in tumors from the patient treatment groups (53% for the gefitinib treated group and 57% for the erlotinib group). c-MET expression was found in nearly half of tested tumors (20/42, 48%). (Figure 1 and Table 2) EGFR, D7S486 and MET FISH analysis EGFR gene amplification ID-8 was found in 4 cases. Two cases showed high polysomy (≥ four copies of the gene in ≥ 40% of cells) and overall, 6/45 (13%) cases were considered as FISH positive. High polysomy of MET gene was detected in 1/43 cases tested. Six cases showed mean copy number of MET gene from 3.11 to 4.05 and were considered as cases with low gain. D7S486 locus deletion was detected in 15/37 (40%) of cases; amplification of the locus was not found in our cohort. (Figure 2 and Table 2) Figure 2 Fluorescence in situ hybridization with gene,
locus and centromeric specific probes. A) Neoplastic nuclei showing EGFR gene amplification (green signals) and polysomy of chromosome 7 (CEP7-orange signals); B) Representative case with normal EGFR gene status; C) MET high level gain (red signals) accompanied by high polysomy of chromosome 7 (CEP7-green signals); D) Normal MET gene status, E) D7S486 locus deletion (red signals); F) D7S486 locus normal status. (Full size images X1000). Correlation of biomarkers with clinical outcome EGFR mutation and FISH status were both associated with DCR. Patients, whose tumors had an EGFR mutation, had a DCR of 45.5% (5/11 patients), whereas among 22 wild type tumors, DCR was observed in only one patient (p = 0.01). Patients with high polysomy and amplification of EGFR gene (n = 6), considered as FISH positive, showed a higher DCR compared with patients with EGFR FISH negative tumors (66.7% versus 12.8%).