Demonstration of EGFR gene copy loss in colorectal carcinomas by fluorescence in situ hybridization (FISH): a surrogate marker for sensitivity to specific anti-EGFR therapy?
OBJECTIVE
To investigate EGFR gene copy number heterogeneity in colorectal carcinomas compared with copy number of chromosome 7 and immunohistochemical expression of the EGFR protein.


RESULTS
Fluorescence in situ hybridization of the EGFR gene and CEP7 was carried out on paraffin-embedded material from 48 rectal carcinomas combined with immunohistochemical detection of EGFR with a polymer detection kit. EGFR gene copy number had a range of 1.4-7.3 with a mean of 2.5. CEP7 copy number had a range of 1.5-6.1 with a mean of 2.5. The EGFR gene/CEP7 ratio ranged from 0.4 to 1.5 with a mean of 0.96. Most cases had a balanced EGFR gene/CEP7 ratio (37 cases = 77%). Copy gain was found in seven cases (15%) with a ratio of up to 1.5, consistent with gain of one EGFR gene copy in one chromosome. Copy loss was found in four cases (8%). All cases with EGFR gene copy loss were immunohistochemically positive.


CONCLUSIONS
Demonstration of EGFR gene copy loss might be a surrogate marker for EGFR mutation/deletion and could be used in a routine setting in pathology departments. Further studies are needed to determine whether this may be used to select patients that might benefit from specific anti-EGFR therapy.
Sauer
T
T
Department of Pathology, Ullevaal University Hospital, Oslo, Norway. torill.sauer@medisin.uio.no
Guren
M G
MG
Noren
T
T
Dueland
S
S
D014408:Biomarkers, Tumor; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002897:Chromosomes, Human, Pair 7; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D018628:Gene Dosage; D015870:Gene Expression; D018773:Genes, erbB-1; D018734:Genes, erbB-2; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D066246:ErbB Receptors