Epidermal growth factor receptor (EGFR) status and K-Ras mutations in colorectal cancer.
BACKGROUND
In advanced colorectal cancer, K-Ras somatic mutations predict resistance to mAbs targeting epidermal growth factor receptor (EGFR). Relationships between K-Ras mutations and EGFR status have not been examined so far. We analyzed relationships between K-Ras mutations and EGFR tumoral status based on EGFR germinal polymorphisms, gene copy number and expression.


METHODS
Eighty colorectal tumors (stage 0-IV) and 39 normal mucosas were analyzed. K-Ras mutations at codons 12 and 13 were detected by a sensitive enrichment double PCR-restriction fragment length polymorphism (RFLP) assay. EGFR gene polymorphisms at positions -216G>T, -191C>A and 497Arg>Lys were analyzed (PCR-RFLP), along with CA repeat polymorphism in intron 1 (fluorescent genotyping) and EGFR gene copy number (PCR amplification). EGFR expression was quantified by Scatchard binding assay.


RESULTS
The number of EGFR high-affinity sites, dissociation constant (Kd), gene copy number, intron 1, -216G>T, -191C>A or 497Lys>Arg genotypes was not different between K-Ras-mutated or K-Ras-non-mutated tumors. No relationship was observed between any of the analyzed EGFR genotypes and EGFR expression. EGFR expression was not related to gene copy number. EGFR gene copy number in tumor and normal tissue was not correlated. The mean value of the tumor/normal mucosa gene copy number ratio was 1.16.


CONCLUSIONS
Present data clearly show that EGFR status is independent of K-Ras mutations in colorectal tumors.
Milano
G
G
Oncopharmacology Unit, EA3836, Centre Antoine-Lacassagne, Nice, France. gerard.milano@nice.fnclcc.fr
Etienne-Grimaldi
M-C
MC
Dahan
L
L
Francoual
M
M
Spano
J-P
JP
Benchimol
D
D
Chazal
M
M
Letoublon
C
C
André
T
T
Gilly
F-N
FN
Delpero
J-R
JR
Formento
J-L
JL
D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D018628:Gene Dosage; D011905:Genes, ras; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012189:Retrospective Studies
D066246:ErbB Receptors