The prognostic value of chromosome 7 polysomy in non-small cell lung cancer patients treated with gefitinib.
BACKGROUND
Specific subpopulations of non-small cell lung cancer (NSCLC) patients defined by clinical features and molecular profiles seem to derive greater benefit from epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, but no general consensus on molecular testing to optimize treatment has emerged. The objective of this study was to evaluate chromosome 7 polysomy and other potential indicators of gefitinib efficacy in advanced NSCLC patients.


METHODS
Paraffin-embedded tumors from 82 patients treated with gefitinib were analyzed by immunohistochemistry for expression of EGFR and other markers, and by fluorescence in situ hybridization for EGFR gene or chromosome copy number. Mutational status was assessed by single-strand conformational polymorphism, sequence-specific polymerase chain reaction, and direct sequencing. Molecular and clinical characteristics were evaluated in relation to objective response (OR), progression-free survival (PFS), and overall survival (OS).


RESULTS
EGFR mutational status (p = 0.002), never smoking (p = 0.052), and chromosome 7 polysomy (p = 0.029) were significant indicators of OR. EGFR mutation, pAKT or PTEN expression, and chromosome 7 polysomy were associated with longer OS. There was a significant difference in OS between the chromosome 7 polysomy groups (p = 0.015) and the groups with both chromosome 7 polysomy and pAkt (p = 0.002) and both chromosome7 polysomy and PTEN (p = 0.04). In a stepwise proportional hazards analysis, chromosome 7 polysomy and PTEN expression were both significantly associated with longer OS (p = 0.004 and 0.017 respectively).


CONCLUSIONS
These results suggest that further study of chromosome 7 polysomy and of pAKT and PTEN expression in patients treated with EGFR tyrosine kinase inhibitors is warranted in developing a clinical test for selecting patients for gefitinib therapy.
Buckingham
Lela E
LE
Rush University Medical Center, Chicago, Illinois 60612, USA. Lela_Buckingham@rush.edu
Coon
John S
JS
Morrison
Larry E
LE
Jacobson
Kristine K B
KK
Jewell
Susan S
SS
Kaiser
Kelly A
KA
Mauer
Ann M
AM
Muzzafar
Tariq
T
Polowy
Clayton
C
Basu
Sanjib
S
Gale
Meryl
M
Villaflor
Victoria M
VM
Bonomi
Philip
P
D000368:Aged; D000782:Aneuploidy; D014408:Biomarkers, Tumor / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D002897:Chromosomes, Human, Pair 7; D004252:DNA Mutational Analysis; D018450:Disease Progression; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D000077156:Gefitinib; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016015:Logistic Models; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib