EGFR alterations in pancreatic ductal adenocarcinoma: a chromogenic in situ hybridization analysis based on tissue microarrays.
OBJECTIVE
To evaluate epidermal growth factor receptor (EGFR) gene status in pancreatic ductal adenocarcinoma correlating the results to protein expression and clinicopathological features


METHODS
Using tissue microarray technology (TMArrayer 100), fifty (n = 50) paraffin-embedded tissue samples of histologically-confirmed primary tumors were cored twice at a diameter of 1 mm and re-embedded into the final recipient block. Immunohistochemistry was performed by the use of anti-EGFR monoclonal antibody (31G7). Also, a chromogenic in situ hybridization protocol was applied based on the use of EGFR gene and chromosome 7 centromeric probes, respectively.


RESULTS
EGFR protein overexpression was observed in 29/50 (58%) cases and correlated to stage (p = 0.001) but not to grade (p = 0.206). EGFR gene analysis identified numerical alterations in 6/50 (12%), including 2 cases characterized by low-level gene amplification and 4 by absence of one allele. Gene status was associated to tumor grade (p = 0.023) and stage (p = 0.02). Chromosome 7 analysis detected aneuploidy in 14 (28%) cases.


CONCLUSIONS
A subset of pancreatic ductal adenocarcinomas (PDACs) is characterized by EGFR gene numerical alterations including sporadic cases of amplification or absence of one allele (maybe due to gene deletion or intragenic point mutation and allelic silence). Those alternative mechanisms maybe influence the efficacy of novel targeted therapeutic strategies based on monoclonal antibodies or intracellular tyrosine-kinase inhibitors in PDACs.
Tsiambas
Evangelos
E
Department of Molecular Pathology, Tissue Microarrays and Image Analysis Lab, 417 VA (NIMTS) Hospital Athens, Greece. tsiambasecyto@yahoo.gr
Karameris
Andreas
A
Lazaris
Andreas C
AC
Talieri
Maroulio
M
Triantafillidis
John K
JK
Cheracakis
Panagiotis
P
Manaios
Loukas
L
Gerontopoulos
Kyriakos
K
Patsouris
Efstratios
E
Lygidakis
Nikolaos J
NJ
D000368:Aged; D000782:Aneuploidy; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002863:Chromogenic Compounds; D002897:Chromosomes, Human, Pair 7; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012189:Retrospective Studies; D046888:Tissue Array Analysis
D002863:Chromogenic Compounds; D066246:ErbB Receptors