Epidermal growth factor receptor overexpression/amplification in adenocarcinomas arising in the gastrointestinal tract.
BACKGROUND
it has been suggested that EGFR might be valuable to select patients for immunotherapy for various types of cancers.


OBJECTIVE
we investigated: a) the gene/proteins alterations in gastrointestinal cancers using immunohistochemistry (IHC) (gene overexpression) and fluorescence in situ hybridisation (FISH) (gene amplification); and b) the associations between EGFR overexpression and amplification and chromosome 7 aneusomy (CEP7) in these cancers.


METHODS
64 tumor specimens were evaluated by IHC and FISH: 17 adenocarcinoma arising in Barrett´s esophagus, 21 stomach cancers, 17 colon cancers, and 9 liver metastasis of colon carcinoma. IHC for EGFR was scored at 4 levels of intensity of membrane staining. EGFR gene in FISH was considered as amplified or not and chromosome 7 (where EGFR is located) as polysomic or disomic. The ratio between EGFR gene and chromosome 7 was performed by FISH and classified the case as gene amplification when the ratio was > 2. Polisomy was identified when the copies of chromosome 7 were > 2 in more than 8% malignant cells.


RESULTS
no difference was found between EGFR gene amplification/protein overexpression according to cancer site. Concerning IHC, most cases were positive for EGFR intensity (84.4%), while only 50% of cases were positive considering a cut-off of 10%. EGFR FISH amplification was found in 4 cases only (6.2%) and FISH CEP7aneusomy in 40.6%. A statistically significant association was found between EGFR protein positivity (IHC) in term of intensity and EGFR gene amplification by FISH (p = 0.003), and between the EGFR protein positivity (IHC) and chromosome 7 aneusomy (FISH) (p = 0.004).


CONCLUSIONS
EGFR amplification assessed by FISH was found in only 4 cases (6.2%) while chromosome 7 aneusomy was identified in 26 (40.6%) cases. IHC proved that EGFR protein overexpression in gastrointestinal cancers is common but FISH assessment showed that EGFR gene amplification is rare. An association was observed between EGFR gene amplification and EGFR protein overexpression in a low number of cases (p = 0.003). A statistically significant association was found between EGFR protein overexpression and chromosome 7 polysomy (p = 0.004).
Department of Pathology, University of Brescia-Spedali Civili, Brescia, Italy.
Elisa
E
Rossi
Vincenzo
V
Villanacci
Cesare
C
Danesino
Francesco
F
Donato
Riccardo
R
Nascimbeni
Gabrio
G
Bassotti
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D000368:Aged; D000782:Aneuploidy; D001471:Barrett Esophagus / Q000235:genetics / Q000473:pathology; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics; D018450:Disease Progression; D066246:ErbB Receptors / Q000096:biosynthesis*; D004938:Esophageal Neoplasms / Q000235:genetics*; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000473:pathology; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D018773:Genes, erbB-1; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008113:Liver Neoplasms / Q000235:genetics / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D011379:Prognosis; D011933:Reagent Kits, Diagnostic; D013274:Stomach Neoplasms / Q000235:genetics
D009363:Neoplasm Proteins; D011933:Reagent Kits, Diagnostic; C512478:EGFR protein, human; D066246:ErbB Receptors